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Keiichi Konoki

Section

Graduate School of Agricultural Science

Job title

Associate Professor

Degree

博士（理学）（東京大学）
修士（理学）（東京大学）

researchmap

https://researchmap.jp/read0140760

J-GLOBAL ID

200901013512696042

Profile

化学の分野に含まれる有機化学の中でも天然物化学と呼ばれる専門領域で基礎研究をしています。最近は学問領域の垣根が低くなり、専門領域をまたいで新たな知識や研究手法を身につけたり、異なる専門領域をもつ研究者と共に共同研究を進めたりするようになりましたが、私は生物化学、分子生物学、薬理学の研究手法を学び、学際研究を進めています。テーマは「海洋生物がつくる、または蓄える二次代謝産物の有毒性のメカニズムを解明」です。二次代謝産物とはタンパク質、炭水化物といった一次代謝産物と分けて考える代謝産物を指して言う言葉ですが、海洋生物がつくる、または蓄える二次代謝産物の中には極めて有毒な物質が存在します。「良薬は口に苦し」ということわざにあるように、蓋を開ければ元々は有毒物質だったという薬が少なからず存在し、それが私の研究対象です。

Research History 5

2008/04 - Present

Graduate School of Agricultural Science, Tohoku University　Associate Professor
2006/07 - 2008/03

Department of Chemistry, Graduate School of Science, Osaka University　Senior Scientist
2003/07 - 2006/04

Department of Pharmacology, University of Washington　Acting Instructor
2000/07 - 2003/06

Department of Pharmacology, University of Washington　Visiting Scientist
1997/01 - 2000/06

Graduate School of Science, The University of Tokyo　助手

Education 4

The University of Tokyo　Graduate School of Science　Department of Chemistry

1996/04 - 1997/01
The University of Tokyo　Graduate School of Science　Department of Chemistry

1993/04 - 1996/03
The University of Tokyo　Graduate School, Division of Science　Department of Chemistry

1991/04 - 1993/03
Waseda University　Faculty of Science and Engineering　Department of Chemistry

1987/04 - 1991/03

Committee Memberships 17

第67回天然有機化合物討論会実行委員

2023/07 - 2025/09
日本農芸化学会　英文誌編集委員会

2021/03 - 2025/02
The Japan Society for Bioscience, Biotechnology, and Agrochemistry (JSBBA)　Committee Member of The 2021 Annual Meeting of JSBBA

2020/03 - 2022/02
日本農芸化学会東北支部　副支部長

2013/05 - 2015/04
日本農芸化学会東北支部　副支部長

2013/05 - 2015/04
日本農芸化学会平成２５年度仙台大会　大会実行委員

2012/04 - 2013/03
日本農芸化学会平成２５年度仙台大会　大会実行委員

2012/04 - 2013/03
平成２６年度日本農芸化学会特別シンポジウム　副支部長

2015/11 -
第７２回日本農芸化学会サイエンスカフェ・第４７回農学カルチャー講座　世話人補佐

2015/11 -
平成２６年度日本農芸化学会特別シンポジウム　副支部長

2015/11 -
第７２回日本農芸化学会サイエンスカフェ・第４７回農学カルチャー講座　世話人補佐

2015/11 -
第７６回日本農芸化学会サイエンスカフェ・第４８回農学カルチャー講座　世話人

2015/02 -
第７６回日本農芸化学会サイエンスカフェ・第４８回農学カルチャー講座　世話人

2015/02 -
日本農芸化学会東北支部2013年度第二回参与会　副支部長

2013/09 -
日本農芸化学会東北支部2013年度第二回参与会　副支部長

2013/09 -
日本農芸化学会東北支部2013年度第一回参与会　副支部長

2013/07 -
日本農芸化学会東北支部2013年度第一回参与会　副支部長

2013/07 -

Show all ︎Show first 5

Professional Memberships 3

日本水産学会

2025/03 - Present
Chemical Society of Japan
Japan Society for Bioscience, Biotechnology, and Agrochemistry

Research Interests 4

Electrophysiology
Voltage-gated sodium channels
Natural Product Chemistry
Target Identification

Research Areas 3

Life sciences / Bioorganic chemistry /
Nanotechnology/Materials / Chemical biology /
Nanotechnology/Materials / Molecular biochemistry /

Awards 6

学生優秀発表賞

2023/12　日本農芸化学会東北支部　オカダ酸結合タンパク質OABP2.1を用いる簡易下痢性貝毒定量法の開発
ポスター発表賞

2023/08　Tohoku University GP-Chem Chemistry Summer School 2023　Evaluation of inhibitory activities of synthetic saxitoxin derivatives to voltage-gated sodium channels
The Excellent Paper Award Published in Bioscience, Biotechnology, & Biochemistry

2023/02　Japan Society for Bioscience, Biotechnology, and Agrochemistry　Mass spectrometry–guided discovery of new analogs of bicyclic phosphotriester salinipostin and evaluation of their monoacylglycerol lipase inhibitory activity
BCSJ Award Article

2022/02　Bulletin of the Chemical Society of Japan　Convergent Synthesis of the WXYZA'B'C'D'E'F' Ring Segment of Maitotoxin
The Best Student Presentation Award

2021/10　The Tohoku Branch of The Japan Society for Bioscience, Biotechnology, and Agrochemistry　Elucidation of MTX-induced Membrane Blebbing
平成25年度日本農芸化学会東北支部奨励賞

2013/10/26　日本農芸化学会東北支部　クロイソカイメンおよびホタテ貝による下痢性貝毒の蓄積機構

Show all ︎Show 5

Papers 107

Total Synthesis and Structural Revision of (±)-Mauritamide B Peer-reviewed

Ryosuke Hirozumi, Yuta Kudo, Yuko Cho, Keiichi Konoki, Mari Yotsu-Yamashita

Journal of Natural Products　2025/02/21

DOI： 10.1021/acs.jnatprod.5c00019 　
Identification of γ-butyrolactone signalling molecules in diverse actinomycetes using resin-assisted isolation and chemoenzymatic synthesis

Yuta Kudo, Keiichi Konoki, Mari Yotsu-Yamashita

RSC Chemical Biology　2025
Publisher: Royal Society of Chemistry (RSC)
DOI： 10.1039/d5cb00007f 　

eISSN： 2633-0679

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γ-Butyrolactone signalling molecules were identified in diverse actinomycetes through resin-assisted isolation, and LCMS analysis using chemoenzymatically synthesized standards.
Intracellular abundance, localization, and enzymatic activity of a saxitoxin biosynthesis enzyme, SxtG, in two sister subclones of the dinoflagellate Alexandrium catenella with extremely different levels of paralytic shellfish toxins

Yuko Cho, Shizu Hidema, Takuo Omura, Shigeki Tsuchiya, Keiichi Konoki, Yasukatsu Oshima, Mari Yotsu-Yamashita

Harmful Algae　139　102723-102723　2024/11
Publisher: Elsevier BV
DOI： 10.1016/j.hal.2024.102723 　

ISSN： 1568-9883
Synthesis of Saxitoxin Biosynthetic Intermediates: Reveal the Mechanism for Formation of its Tricyclic Skeleton in Biosynthesis Peer-reviewed

Ryosuke Hirozumi, Mayu Hakamada, Takashi Minowa, Yuko Cho, Yuta Kudo, Keiichi Konoki, Yasukatsu Oshima, Kazuo Nagasawa, Mari Yotsu-Yamashita

Chemistry - An Asian Journal　2024/09

DOI： 10.1002/asia.202400834 　
Assay for okadaic acid O-acyl transferase using HPLC-FLD Peer-reviewed

Masato Terauchi, Yuki Komazaki, Atsushi Yoshino, Yuko Cho, Yuta Kudo, Mari Yotsu-Yamashita, Keiichi Konoki

Bioscience, Biotechnology, and Biochemistry　88　(9)　999-1006　2024/06/17
Publisher: Oxford University Press (OUP)
DOI： 10.1093/bbb/zbae085 　

eISSN： 1347-6947

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ABSTRACT Dinophysistoxin 1 (DTX1, 1) and okadaic acid (OA, 2), produced by the dinoflagellates Dinophysis spp. and Prorocentrum spp., are primary diarrhetic shellfish toxins (DSTs), which may cause gastric illness in people consuming such as bivalves. Both compounds convert to dinophysistoxin 3 (DTX3, 3; generic name for 1 and 2 with fatty acids conjugated at 7-OH) in bivalves. The enzyme okadaic acid O-acyl transferase (OOAT) is a membrane protein found in the microsomes of the digestive glands of bivalves. In this study, we established an in vitro enzymatic conversion reaction using 4-nitro-2,1,3-benzoxadiazole (NBD)-OA (4), an OA derivative conjugated with (R)-(-)-4-nitro-7-(3-aminopyrrolidin-1-yl)-2,1,3-benzoxadiazole (NBD-APy) on 1-CO2H, as a substrate. We detected the enzymatically produced 3, NBD-7-O-palmitoyl-OA (NBD-Pal-OA), using high-performance liquid chromatography-fluorescence detection. We believe that an OOAT assay using 4 will facilitate the fractionation and isolation of OOAT in the future.
Synthesis and Identification of decarbamoyloxySaxitoxins in Toxic Microalgae and their Reactions with the Oxygenase, SxtT, Reveal Saxitoxin Biosynthesis

Mayu Hakamada, Chihiro Tokairin, Hayate Ishizuka, Kanna Adachi, Toma Osawa, Shiori Aonuma, Ryosuke Hirozumi, Shigeki Tsuchiya, Yuko Cho, Yuta Kudo, Keiichi Konoki, Yasukatsu Oshima, Kazuo Nagasawa, Mari Yotsu-Yamashita

Chemistry – A European Journal　2024/01/25
Publisher: Wiley
DOI： 10.1002/chem.202304238 　

ISSN： 0947-6539

eISSN： 1521-3765

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Saxitoxin (STX, 1) is a representative compound of paralytic shellfish toxins (PSTs) that are produced by marine dinoflagellates and freshwater cyanobacteria. Although several pathways have been proposed for the biosynthesis of STX, the order of ring and side chain hydroxylation, and formation of the tricyclic skeleton have not been well established. In this study, 12,12‐dideoxy‐decarbamoyloxySTX (dd‐doSTX, 2), the most reduced STX analogue having the tricyclic skeleton, and its analogues, 12β‐deoxy‐doSTX (12β‐d‐doSTX, 3), 12α‐deoxy‐doSTX (12α‐d‐doSTX, 4), and doSTX (5), were synthesized, and these compounds were screened in the toxic microalgae using high‐resolution LCMSMS. dd‐doSTX (2) and 12β‐d‐doSTX (3) were identified in the PSTs‐producing dinoflagellates (Alexandrium catenella, A. pacificum, and/or Gymnodinium catenatum) and in the cyanobacterium Dolichospermum circinale (TA04). doSTX (5), previously isolated from the dinoflagellate G. catenatum, was also identified in D. circinale (TA04). Furthermore, the conversion of 2 to 3, and 4 to 5, by SxtT with VanB, a reported Rieske oxygenase and its redox partner in STX biosynthesis, was confirmed. These results support that 2 is a possible biosynthetic precursor of STX, and that ring and side‐chain hydroxylations proceed after cyclization.
The quite low cross-reactivity of Kawatsu's anti-tetrodotoxin monoclonal antibody to 5,6,11-trideoxytetrodotoxin, 11-nortetrodotoxin-6(S)-ol, and 11-oxotetrodotoxin, the major tetrodotoxin analogues in pufferfish

Keita Yamaki, Kyoka Sato, Yuta Kudo, Yuko Cho, Keiichi Konoki, Tomohiro Takatani, Osamu Arakawa, Kentaro Kawatsu, Mari Yotsu-Yamsahita

Toxicon　107081-107081　2023/03
Publisher: Elsevier BV
DOI： 10.1016/j.toxicon.2023.107081 　

ISSN： 0041-0101
Metabolic inhibitor induces dynamic changes in saxitoxin biosynthesis and metabolism in the dinoflagellate Alexandrium pacificum (Group IV) under in vivo labeling condition

Yuko Cho, Shigeki Tsuchiya, Takuo Omura, Kazuhiko Koike, Keiichi Konoki, Yasukatsu Oshima, Mari Yotsu-Yamashita

Harmful Algae　122　102372-102372　2023/02
Publisher: Elsevier BV
DOI： 10.1016/j.hal.2022.102372 　

ISSN： 1568-9883
State-Dependent Inhibition of Voltage-Gated Sodium Channels in Neuroblastoma Neuro-2A Cells by Arachidonic Acid from Halichondria okadai

Osamu Chiba, Noriko Shimada, Shutaro Yoshio, Yuta Kudo, Yuko Cho, Mari Yotsu-Yamashita, Keiichi Konoki

Chemical Research in Toxicology　35　(11)　1950-1961　2022/11/21
Publisher: American Chemical Society (ACS)
DOI： 10.1021/acs.chemrestox.2c00062 　

ISSN： 0893-228X

eISSN： 1520-5010
Isolation and Biological Activity of 9-epiTetrodotoxin and Isolation of Tb-242B, Possible Biosynthetic Shunt Products of Tetrodotoxin from Pufferfish

Yuji Yaegashi, Yuta Kudo, Nozomi Ueyama, Ken-ichi Onodera, Yuko Cho, Keiichi Konoki, Mari Yotsu-Yamashita

Journal of Natural Products　85　(9)　2199-2206　2022/09/23
Publisher: American Chemical Society (ACS)
DOI： 10.1021/acs.jnatprod.2c00588 　

ISSN： 0163-3864

eISSN： 1520-6025
4. Biosynthesis of paralytic shellfish toxins in dinoflagellates

YUKO CHO, SHIZU HIDEMA, TAKUO OMURA, SHIGEKI TSUCHIYA, KAZUHIKO KOIKE, KANAE KOIKE, HIROSHI OIKAWA, KEIICHI KONOKI, YASUKATSU OSHIMA, MARI YOTSU-YAMASHITA

NIPPON SUISAN GAKKAISHI　88　(5)　424-424　2022/09/15
Publisher: Japanese Society of Fisheries Science
DOI： 10.2331/suisan.wa2978-5 　

ISSN： 0021-5392

eISSN： 1349-998X
3. Prediction of biosynthetic pathways of the pufferfish toxin, tetrodotoxin

MARI YOTSU-YAMASHITA, YUTA KUDO, NOZOMI UEYAMA, CHARLES T. HANIFIN, SATOSHI NUMANO, YUKO CHO, KEIICHI KONOKI

NIPPON SUISAN GAKKAISHI　88　(5)　423-423　2022/09/15
Publisher: Japanese Society of Fisheries Science
DOI： 10.2331/suisan.wa2978-4 　

ISSN： 0021-5392

eISSN： 1349-998X
Nontoxic Enantiomeric Reference Materials for Saxitoxins

Ryuichi Watanabe, Yuka Takayanagi, Osamu Chiba, Shota Itoda, Hayate Ishizuka, Minami Odagi, Mayu Ozawa, Hajime Uchida, Ryoji Matsushima, Keiichi Konoki, Mari Yotsu-Yamashita, Kazuo Nagasawa, Toshiyuki Suzuki

Analytical Chemistry　2022/08/07
Publisher: American Chemical Society (ACS)
DOI： 10.1021/acs.analchem.2c00836 　

ISSN： 0003-2700

eISSN： 1520-6882
Mass spectrometry–guided discovery of new analogues of bicyclic phosphotriester salinipostin and evaluation of their monoacylglycerol lipase inhibitory activity

Yuta Kudo, Keiichi Konoki, Mari Yotsu-Yamashita

Bioscience, Biotechnology, and Biochemistry　86　(10)　1333-1342　2022/08/02
Publisher: Oxford University Press (OUP)
DOI： 10.1093/bbb/zbac131 　

eISSN： 1347-6947

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Abstract Natural products containing the highly unusual phosphotriester ring are known to be potent serine hydrolase inhibitors. The long-chain bicyclic enol-phosphotriester salinipostins (SPTs) from the marine actinomycete Salinispora have been identified as selective antimalarial agents. A potential regulatory function has been suggested for phosphotriesters based on their structural relationship with actinomycete signaling molecules and the prevalence of spt-like biosynthetic gene clusters across actinomycetes. In this study, we established a mass spectrometry–guided screening method for phosphotriesters focusing on their characteristic fragment ions. Applying this screening method to the SPT producer Salinispora tropica CNB-440, new SPT analogues (4–6) were discovered and their structures were elucidated by spectroscopic analyses. Previously known and herein-identified SPT analogues inhibited the activity of human monoacylglycerol lipase (MAGL), a key serine hydrolase in the endocannabinoid system, in the nanomolar range. Our method could be applied to the screening of phosphotriesters, potential serine hydrolase inhibitors and signaling molecules.
First Identification of 12β-Deoxygonyautoxin 5 (12α-Gonyautoxinol 5) in the Cyanobacterium Dolichospermum circinale (TA04) and 12β-Deoxysaxitoxin (12α-Saxitoxinol) in D. circinale (TA04) and the Dinoflagellate Alexandrium pacificum (Group IV) (120518KureAC) Peer-reviewed

Michiru Akamatsu, Ryosuke Hirozumi, Yuko Cho, Yuta Kudo, Keiichi Konoki, Yasukatsu Oshima, Mari Yotsu-Yamashita

Marine Drugs　20　(3)　166-166　2022/02/25
Publisher: MDPI AG
DOI： 10.3390/md20030166 　

eISSN： 1660-3397

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Saxitoxin and its analogues, paralytic shellfish toxins (PSTs), are potent and specific voltage-gated sodium channel blockers. These toxins are produced by some species of freshwater cyanobacteria and marine dinoflagellates. We previously identified several biosynthetic intermediates of PSTs, as well as new analogues, from such organisms and proposed the biosynthetic and metabolic pathways of PSTs. In this study, 12β-deoxygonyautoxin 5 (12α-gonyautoxinol 5 = gonyautoxin 5-12(R)-ol) was identified in the freshwater cyanobacterium, Dolichospermum circinale (TA04), and 12β-deoxysaxitoxin (12α-saxitoxinol = saxitoxin-12(R)-ol) was identified in the same cyanobacterium and in the marine dinoflagellate Alexandrium pacificum (Group IV) (120518KureAC) for the first time from natural sources. The authentic standards of these compounds and 12α-deoxygonyautoxin 5 (12β-gonyautoxinol 5 = gonyautoxin 5-12(S)-ol) were prepared by chemical derivatization from the major PSTs, C1/C2, produced in D. circinale (TA04). These standards were used to identify the deoxy analogues by comparing the retention times and MS/MS spectra using high-resolution LC-MS/MS. Biosynthetic or metabolic pathways for these analogues have also been proposed based on their structures. The identification of these compounds supports the α-oriented stereoselective oxidation at C12 in the biosynthetic pathway towards PSTs.
Convergent Synthesis of the WXYZA′B′C′D′E′F′ Ring Segment of Maitotoxin Peer-reviewed

Keitaro Umeno, Hisaaki Onoue, Keiichi Konoki, Kohei Torikai, Yoko Yasuno, Masayuki Satake, Tohru Oishi

Bulletin of the Chemical Society of Japan　95　(2)　325-330　2022/02/15
Publisher: The Chemical Society of Japan
DOI： 10.1246/bcsj.20210397 　

ISSN： 0009-2673

eISSN： 1348-0634
Two new skeletal analogues of saxitoxin found in the scallop, Patinopecten yessoensis, as possible metabolites of paralytic shellfish toxins Peer-reviewed

Satoshi Numano, Yuta Kudo, Yuko Cho, Keiichi Konoki, Yoshimasa Kaga, Kazuo Nagasawa, Mari Yotsu-Yamashita

Chemosphere　278　130224-130224　2021/03
Publisher: Elsevier BV
DOI： 10.1016/j.chemosphere.2021.130224 　

ISSN： 0045-6535
Preparation of domoic acid analogues using a bioconversion system, and their toxicity in mice

Yukari Maeno, Yuichi Kotaki, Ryuta Terada, Masafumi Hidaka, Yuko Cho, Keiichi Konoki, Mari Yotsu-Yamashita

Organic & Biomolecular Chemistry　2021
Publisher: Royal Society of Chemistry (RSC)
DOI： 10.1039/d1ob01378e 　

ISSN： 1477-0520

eISSN： 1477-0539

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Domoic acid analogues were prepared by chemical synthesis and enzymatic stereoselective cyclization using a bioconversion system. The 7’-carbonyl group in the terminus of the side chain was suggested to be crucial for the toxicity in mice.
SxtA localizes to chloroplasts and changes to its 3′UTR may reduce toxin biosynthesis in non-toxic Alexandrium catenella (Group I)✰

Yuko Cho, Shizu Hidema, Takuo Omura, Kazuhiko Koike, Kanae Koike, Hiroshi Oikawa, Keiichi Konoki, Yasukatsu Oshima, Mari Yotsu-Yamashita

Harmful Algae　101　101972-101972　2021/01
Publisher: Elsevier BV
DOI： 10.1016/j.hal.2020.101972 　

ISSN： 1568-9883
生物が作り出す毒「どくどくしくない毒のはなし」 Invited

山下まり, 此木敬一, 稲垣英利, 森直樹, 森晢

化学と生物　58　(2)　111-119　2020/02
Temporal Variation of the Profile and Concentrations of Paralytic Shellfish Toxins and Tetrodotoxin in the Scallop, Patinopecten yessoensis, Cultured in a Bay of East Japan International-journal Peer-reviewed

Satoshi Numano, Yuta Kudo, Yuko Cho, Keiichi Konoki, Mari Yotsu-Yamashita

Marine Drugs　17　(12)　653　2019/11

DOI： 10.3390/md17120653 　

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Paralytic shellfish toxins (PSTs) are the major neurotoxic contaminants of edible bivalves in Japan. Tetrodotoxin (TTX) was recently detected in bivalve shellfish around the world, drawing widespread attention. In Japan, high levels of TTX were reported in the digestive gland of the scallop, Patinopecten yessoensis, in 1993; however, no new data have emerged since then. In this study, we simultaneously analyzed PSTs and TTX in scallops cultured in a bay of east Japan using hydrophilic interaction chromatography (HILIC)-MS/MS. These scallops were temporally collected from April to December 2017. The highest concentration of PSTs (182 µmol/kg, total congeners) in the hepatopancreas was detected in samples collected on May 23, lined to the cell density of the dinoflagellate, Alexandrium tamarense, in seawater around the scallops, whereas the highest concentration of TTX (421 nmol/kg) was detected in samples collected on August 22. Contrary to the previous report, temporal variation of the PSTs and TTX concentrations did not coincide. The highest concentration of TTX in the entire edible tissues was 7.3 µg/kg (23 nmol/kg) in samples obtained on August 22, which was lower than the European Food Safety Authority (EFSA)-proposed threshold, 44 µg TTX equivalents/kg shellfish meat. In addition, 12β-deoxygonyautoxin 3 was firstly identified in scallops.
Synthesis of C12‐keto saxitoxin derivatives with unusual inhibitory activity against voltage‐gated sodium channels Kanna Adachi,] Tomoshi Yamada, Hayate Ishizuka, Mana Oki,Shunsuke Tsunogae, Noriko Shimada, Osamu Chiba, Tatsuya Orihara, Masafumi Hidaka, T Peer-reviewed

Kanna Adachi, Tomoshi Yamada, Hayate Ishizuka, Mana Oki, Shunsuke Tsunogae, Noriko Shimada, Osamu Chiba, Tatsuya Orihara, Masafumi Hidaka, Takatsugu Hirokawa, Minami Odagi, Keiichi Konoki, Mari Yotsu-Yamashita, Kazuo Nagasawa

Chemistry - A European Journal　26　2025-2033　2019/11
Identification of a Novel Saxitoxin Analogue, 12β-Deoxygonyautoxin 3, in the Cyanobacterium, Anabaena circinalis (TA04) Peer-reviewed

Minowa, Cho, Oshima, Konoki, Yotsu-Yamashita

Toxins　11　(9)　539-539　2019/09/16
Publisher: MDPI AG
DOI： 10.3390/toxins11090539 　

eISSN： 2072-6651

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Saxitoxin (STX) and its analogues, the potent voltage-gated sodium channel blockers, are biosynthesized by freshwater cyanobacteria and marine dinoflagellates. We previously identified several biosynthetic intermediates in the extract of the cyanobacterium, Anabaena circinalis (TA04), that are primarily produced during the early and middle stages in the biosynthetic pathway to produce STX. These findings allowed us to propose a putative biosynthetic pathway responsible for STX production based on the structures of these intermediates. In the present study, we identified 12β-deoxygonyautoxin 3 (12β-deoxyGTX3), a novel STX analogue produced by A. circinalis (TA04), by comparing the retention time and MS/MS fragmentation pattern with those of synthetic standards using LC–MS. The presence of this compound in A. circinalis (TA04) is consistent with stereoselective enzymatic oxidations at C11 and C12, and 11-O-sulfation, during the late stage of STX biosynthesis, as proposed in previous studies.
Molecular Determinants of Brevetoxin Binding to Voltage-Gated Sodium Channels Peer-reviewed

Keiichi Konoki, Daniel G. Baden, Todd Scheuer, William A. Catterall

Toxins　11　(9)　513-513　2019/09/03
Publisher: MDPI AG
DOI： 10.3390/toxins11090513 　

eISSN： 2072-6651

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Brevetoxins are produced by dinoflagellates such as Karenia brevis in warm-water red tides and cause neurotoxic shellfish poisoning. They bind to voltage-gated sodium channels at neurotoxin receptor 5, making the channels more active by shifting the voltage-dependence of activation to more negative potentials and by slowing the inactivation process. Previous work using photoaffinity labeling identified binding to the IS6 and IVS5 transmembrane segments of the channel α subunit. We used alanine-scanning mutagenesis to identify molecular determinants for brevetoxin binding in these regions as well as adjacent regions IVS5-SS1 and IVS6. Most of the mutant channels containing single alanine substitutions expressed functional protein in tsA-201 cells and bound to the radioligand [42-3H]-PbTx3. Binding affinity for the great majority of mutant channels was indistinguishable from wild type. However, transmembrane segments IS6, IVS5 and IVS6 each contained 2 to 4 amino acid positions where alanine substitution resulted in a 2–3-fold reduction in brevetoxin affinity, and additional mutations caused a similar increase in brevetoxin affinity. These findings are consistent with a model in which brevetoxin binds to a protein cleft comprising transmembrane segments IS6, IVS5 and IVS6 and makes multiple distributed interactions with these α helices. Determination of brevetoxin affinity for Nav1.2, Nav1.4 and Nav1.5 channels showed that Nav1.5 channels had a characteristic 5-fold reduction in affinity for brevetoxin relative to the other channel isoforms, suggesting the interaction with sodium channels is specific despite the distributed binding determinants.
Possible metabolites and biosynthetic products that suggest common mechanism for formation of the pyrrolidine ring in kainoids International-journal Peer-reviewed

Maeno, Y, Terada, R, Kotaki, Y, Cho, Y, Konoki, K, Yotsu-Yamashita, M

Journal of Natural Products　82　(6)　1627-1633　2019/06

DOI： 10.1021/acs.jnatprod.9b00128 　

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Four kainic acid (KA, 1)-related compounds, 4-hydroxykainic acid (2), allo-4-hydroxykainic acid (3), N-dimethylallyl-l-glutamic acid (4), and N-dimethylallyl- threo-3-hydroxyglutamic acid (5), were isolated from the red alga Digenea simplex. The structures of these compounds were elucidated using spectroscopic methods. Compounds 2 and 3 are possible oxidative metabolites of KA and allo-KA (6), respectively. Compound 4 was recently reported as the biosynthetic precursor of KA, but the absolute configuration of 4 has not been previously determined. Herein, we determined the absolute configuration of 4 as 2( S) using advanced Marfey's method. Compound 5 is similar to N-geranyl-3( R)-hydroxy-l-glutamic acid (8), which was previously identified in a domoic acid (DA)-containing red alga. Compounds 5 and 8 are predicted to be biosynthetic byproducts of the radical-mediated cyclization reaction to form the pyrrolidine rings of KA and DA, respectively. Furthermore, the toxicities of 1-5 in mice were examined by intracerebroventricular injection. The toxicity of 2 was less than that of KA; however, the mice injected with 2 showed symptoms similar to those induced by KA, while 3-5 did not induce typical symptoms of KA in mice.
Possible biosynthetic products and metabolites of kainic acid from the red alga, Digenea simplex, and their biological activity Peer-reviewed

Yukari Maeno, Ryuta Terada, Yuichi Kotaki, Yuko Cho, Keiichi Konoki, Mari Yotsu-Yamashita

Journal of Natural Products　82　1627-1633　2019/05
Metabolomic study of saxitoxin analogues and biosynthetic intermediates in dinoflagellates using ¹⁵N-labelled sodium nitrate as a nitrogen source. Peer-reviewed

Cho Y, Tsuchiya S, Omura T, Koike K, Oikawa H, Konoki K, Oshima Y, Yotsu-Yamashita M

Scientific reports　9　(1)　3460　2019/03

DOI： 10.1038/s41598-019-39708-y 　
Six domoic acid related compounds from the red alga, Chondria armata, and domoic acid biosynthesis by the diatom, Pseudo-nitzschia multiseries Peer-reviewed

Yukari Maeno, Yuichi Kotaki, Ryuta Terada, Yuko Cho, Keiichi Konoki, Mari Yotsu-Yamashita

Scientific Reports　8　(1)　356　2018/12/01
Publisher: Nature Publishing Group
DOI： 10.1038/s41598-017-18651-w 　

ISSN： 2045-2322
Isolation and structure determination of lysiformine from bacteria associated with marine sponge Halichondria okadai Peer-reviewed

Sou Kikuchi, Kayo Okada, Yuko Cho, Shinichiro Yoshida, Eunsang Kwon, Mari Yotsu-Yamashita, Keiichi Konoki

Tetrahedron　74　(27)　3742-3747　2018/07/05
Publisher: Elsevier Ltd
DOI： 10.1016/j.tet.2018.05.049 　

ISSN： 1464-5416 0040-4020
Pufferfish Saxitoxin and Tetrodotoxin Binding Protein (PSTBP) Analogues in the Blood Plasma of the Pufferfish Arothron nigropunctatus, A. hispidus, A. manilensis, and Chelonodon patoca. Peer-reviewed

Yotsu-Yamashita M, Nagaoka Y, Muramoto K, Cho Y, Konoki K

Marine drugs　16　(7)　2018/06

DOI： 10.3390/md16070224 　
Spiro Bicyclic Guanidino Compounds from Pufferfish: Possible Biosynthetic Intermediates of Tetrodotoxin in Marine Environments Peer-reviewed

Nozomi Ueyama, Keita Sugimoto, Yuta Kudo, Ken-Ichi Onodera, Yuko Cho, Keiichi Konoki, Toshio Nishikawa, Mari Yotsu-Yamashita

Chemistry - A European Journal　24　(28)　7250-7258　2018/05/17
Publisher: Wiley-VCH Verlag
DOI： 10.1002/chem.201801006 　

ISSN： 1521-3765 0947-6539
Differential binding of tetrodotoxin and its derivatives to voltage-sensitive sodium channel subtypes (Na(v)1.1 to Na(v)1.7) Peer-reviewed

Tadaaki Tsukamoto, Yukie Chiba, Minoru Wakamori, Tomoshi Yamada, Shunsuke Tsunogae, Yuko Cho, Ryo Sakakibara, Takuya Imazu, Shouta Tokoro, Yoshiki Satake, Masaatsu Adachi, Toshio Nishikawa, Mari Yotsu-Yamashita, Keiichi Konoki

BRITISH JOURNAL OF PHARMACOLOGY　174　(21)　3881-3892　2017/11

DOI： 10.1111/bph.13985 　

ISSN： 0007-1188

eISSN： 1476-5381
Dietary administration of tetrodotoxin and its putative biosynthetic intermediates to the captive-reared non-toxic Japanese fire-bellied newt, Cynops pyrrhogaster Peer-reviewed

Yuta Kudo, Chikafumi Chiba, Keiichi Konoki, Yuko Cho, Mari Yotsu-Yamashita

TOXICON　137　78-82　2017/10

DOI： 10.1016/j.toxicon.2017.07.016 　

ISSN： 0041-0101
フグの新規スピロ環状グアニジノ化合物の単離,構造決定と海産テトロドトキシンの生合成経路の推定 Peer-reviewed

上山望, 杉本敬太, 工藤雄大, 長由扶子, 此木敬一, 西川俊夫, 山下まり

第59回天然有機化合物討論会講演要旨集　59　597-602　2017/09/23

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学会紀要
化学合成に基づいたマイトトキシンの構造活性相関研究 Peer-reviewed

尾上久晃, 石川絵理奈, 丸林里帆, 此木敬一, 鳥飼浩平, 海老根真琴, 大石徹

第59回天然有機化合物討論会講演要旨集　59　201-206　2017/09/23

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学会紀要
Syntheses and Biological Activities of the LMNO, ent-LMNO, and NOPQR(S) Ring Systems of Maitotoxin Peer-reviewed

Hisaaki Onoue, Riho Marubayashi, Erina Ishikawa, Keiichi Konoki, Kohei Torikai, Makoto Ebine, Michio Murata, Tohru Oishi

JOURNAL OF ORGANIC CHEMISTRY　82　(18)　9595-9618　2017/09

DOI： 10.1021/acs.joc.7b01658 　

ISSN： 0022-3263
Synthesis and Identification of Key Biosynthetic Intermediates for the Formation of the Tricyclic Skeleton of Saxitoxin Peer-reviewed

Shigeki Tsuchiya, Yuko Cho, Renpei Yoshioka, Keiichi Konoki, Kazuo Nagasawa, Yasukatsu Oshima, Mari Yotsu-Yamashita

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION　56　(19)　5327-5331　2017/05

DOI： 10.1002/anie.201612461 　

ISSN： 1433-7851

eISSN： 1521-3773
Inhibition of veratridine-induced delayed inactivation of the voltage-sensitive sodium channel by synthetic analogs of crambescin B Peer-reviewed

Tadaaki Tsukamoto, Yukie Chiba, Atsuo Nakazaki, Yuki Ishikawa, Yoshiki Nakane, Yuko Cho, Mad Yotsu-Yamashita, Toshio Nishikawa, Minoru Wakamori, Keiichi Konoki

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS　27　(5)　1247-1251　2017/03

DOI： 10.1016/j.bmcl.2017.01.054 　

ISSN： 0960-894X

eISSN： 1464-3405
A new sarasinoside congener, sarasinoside M-2, from a marine sponge collected in the Solomon Islands Peer-reviewed

Clyde Gorapava Puilingi, Yuta Kudo, Yuko Cho, Keiichi Konoki, Mari Yotsu-Yamashita

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY　81　(2)　222-225　2017/02

DOI： 10.1080/09168451.2016.1246172 　

ISSN： 0916-8451

eISSN： 1347-6947
Column switching combined with hydrophilic interaction chromatography-tandem mass spectrometry for the analysis of saxitoxin analogues, and their biosynthetic intermediates in dinoflagellates Peer-reviewed

Yuko Cho, Shigeki Tsuchiya, Renpei Yoshioka, Takuo Omura, Keiichi Konoki, Yasukatsu Oshima, Mari Yotsu-Yamashita

JOURNAL OF CHROMATOGRAPHY A　1474　109-120　2016/11

DOI： 10.1016/j.chroma.2016.10.065 　

ISSN： 0021-9673

eISSN： 1873-3778
The voltage-gated sodium ion channel inhibitory activities of a new tetrodotoxin analogue, 4,4a-anhydrotetrodotoxin, and three other analogues evaluated by colorimetric cell-based assay Peer-reviewed

Shogo Saruhashi, Keiichi Konoki, Mari Yotsu-Yamashita

TOXICON　119　72-76　2016/09

DOI： 10.1016/j.toxicon.2016.05.012 　

ISSN： 0041-0101
Diastereoselective Ring-Closing Metathesis as a Means to Construct Medium-Sized Cyclic Ethers: Application to the Synthesis of a Photoactivatable Gambierol Derivative Peer-reviewed

Yu Onodera, Kazuaki Hirota, Yuto Suga, Keiichi Konoki, Mari Yotsu-Yamashita, Makoto Sasaki, Haruhiko Fuwa

JOURNAL OF ORGANIC CHEMISTRY　81　(18)　8234-8252　2016/09

DOI： 10.1021/acs.joc.6b01302 　

ISSN： 0022-3263
Effect of carbon chain length in acyl coenzyme A on the efficiency of enzymatic transformation of okadaic acid to 7-O-acyl okadaic acid Peer-reviewed

Sachie Furumochi, Tatsuya Onoda, Yuko Cho, Haruhiko Fuwa, Makoto Sasaki, Mari Yotsu-Yamashita, Keiichi Konoki

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS　26　(13)　2992-2996　2016/07

DOI： 10.1016/j.bmcl.2016.05.027 　

ISSN： 0960-894X

eISSN： 1464-3405
Biosynthetic route towards saxitoxin and shunt pathway Peer-reviewed

Shigeki Tsuchiya, Yuko Cho, Keiichi Konoki, Kazuo Nagasawa, Yasukatsu Oshima, Mari Yotsu-Yamashita

SCIENTIFIC REPORTS　6　20340　2016/02

DOI： 10.1038/srep20340 　

ISSN： 2045-2322
Cyclic Guanidine Compounds from Toxic Newts Support the Hypothesis that Tetrodotoxin is Derived from a Monoterpene Peer-reviewed

Yuta Kudo, Takeshi Yasumoto, Dietrich Mebs, Yuko Cho, Keiichi Konoki, Mari Yotsu-Yamashita

Angewandte Chemie - International Edition　55　(30)　8728-8731　2016
Publisher: Wiley-VCH Verlag
DOI： 10.1002/anie.201602971 　

ISSN： 1521-3773 1433-7851
Identification of okadaic acid binding protein 2 in reconstituted sponge cell clusters from Halichondria okadai and its contribution to the detoxification of okadaic acid Peer-reviewed

Keiichi Konoki, Kayo Okada, Mami Kohama, Hiroki Matsuura, Kaori Saito, Yuko Cho, Goh Nishitani, Tomofumi Miyamoto, Seketsu Fukuzawa, Kazuo Tachibana, Mari Yotsu-Yamashita

TOXICON　108　38-45　2015/12

DOI： 10.1016/j.toxicon.2015.09.026 　

ISSN： 0041-0101
The presence of 12 beta-deoxydecarbamoylsaxitoxin in the Japanese toxic dinoflagellate Alexandrium determined by simultaneous analysis for paralytic shellfish toxins using HILIC-LC-MS/MS Peer-reviewed

Yuko Cho, Shigeki Tsuchiya, Renpei Yoshioka, Takuo Omura, Keiichi Konoki, Yasukatsu Oshima, Mari Yotsu-Yamashita

HARMFUL ALGAE　49　58-67　2015/11

DOI： 10.1016/j.hal.2015.09.003 　

ISSN： 1568-9883

eISSN： 1878-1470
Tetrodotoxin and Its Analogues in the Pufferfish Arothron hispidus and A-nigropunctatus from the Solomon Islands: A Comparison of Their Toxin Profiles with the Same Species from Okinawa, Japan Peer-reviewed

Clyde Gorapava Puilingi, Yuta Kudo, Yuko Cho, Keiichi Konoki, Mari Yotsu-Yamashita

TOXINS　7　(9)　3436-3454　2015/09

DOI： 10.3390/toxins7093436 　

ISSN： 2072-6651
Crystal Structure of Okadaic Acid Binding Protein 2.1: A Sponge Protein Implicated in Cytotoxin Accumulation Peer-reviewed

Haruhiko Ehara, Marie Makino, Koichiro Kodama, Keiichi Konoki, Takuhiro Ito, Shun-ichi Sekine, Seketsu Fukuzawa, Shigeyuki Yokoyama, Kazuo Tachibana

CHEMBIOCHEM　16　(10)　1435-1439　2015/07

DOI： 10.1002/cbic.201500141 　

ISSN： 1439-4227

eISSN： 1439-7633
Confirmation of the absence of tetrodotoxin and its analogues in the juveniles of the Japanese fire-bellied newt, Cynops pyrrhogaster, captive-reared from eggs in the laboratory using HILIC-LC-MS Peer-reviewed

Yuta Kudo, Chikafumi Chiba, Keiichi Konoki, Yuko Cho, Mad Yotsu-Yamashita

TOXICON　101　101-105　2015/07

DOI： 10.1016/j.toxicon.2015.05.008 　

ISSN： 0041-0101
Synthesis of a Tricyclic Bisguanidine Compound Structurally Related to Saxitoxin and its Identification in Paralytic Shellfish Toxin-Producing Microorganisms Peer-reviewed

Shigeki Tsuchiya, Yuko Cho, Keiichi Konoki, Kazuo Nagasawa, Yasukatsu Oshima, Mari Yotsu-Yamashita

CHEMISTRY-A EUROPEAN JOURNAL　21　(21)　7835-7840　2015/05

DOI： 10.1002/chem.201500064 　

ISSN： 0947-6539

eISSN： 1521-3765
Evaluation of gambierol and its analogs for their inhibition of human K(v)1.2 and cytotoxicity Peer-reviewed

Keiichi Konoki, Yuto Suga, Haruhiko Fuwa, Mari Yotsu-Yamashita, Makoto Sasaki

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS　25　(3)　514-518　2015/02

DOI： 10.1016/j.bmcl.2014.12.022 　

ISSN： 0960-894X

eISSN： 1464-3405
Synthesis and Biological Activity of the QRS Ring System of Maitotoxin Peer-reviewed

Hisaaki Onoue, Tomomi Baba, Keiichi Konoki, Kohei Torikai, Makoto Ebine, Tohru Oishi

CHEMISTRY LETTERS　43　(12)　1904-1906　2014/12

DOI： 10.1246/cl.140789 　

ISSN： 0366-7022

eISSN： 1348-0715
C5-C10 Directly Bonded Tetrodotoxin Analogues: Possible Biosynthetic Precursors of Tetrodotoxin From Newts Peer-reviewed

Yuta Kudo, Yoko Yamashita, Dietrich Mebs, Yuko Cho, Keiichi Konoki, Takeshi Yasumoto, Mari Yotsu-Yamashita

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION　53　(52)　14546-14549　2014/12

DOI： 10.1002/anie.201408913 　

ISSN： 1433-7851

eISSN： 1521-3773
Expression of recombinant alpha and beta tubulins from the yew Taxus cuspidata and analysis of the microtubule assembly in the presence of taxol Peer-reviewed

Yuma Kudo, Akihiro Abe, Kumiko Ito, Yuko Cho, Mari Yotsu-Yamashita, Keiichi Konoki

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY　78　(11)　1887-1894　2014/11

DOI： 10.1080/09168451.2014.940837 　

ISSN： 0916-8451

eISSN： 1347-6947
Synthesis and Biological Evaluation of QRSTUVWXYZA ' Domains of Maitotoxin Peer-reviewed

K. C. Nicolaou, Philipp Heretsch, Tsuyoshi Nakamura, Anna Rudo, Michio Murata, Keiichi Konoki

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY　136　(46)　16444-16451　2014/11

DOI： 10.1021/ja509829e 　

ISSN： 0002-7863
クロイソカイメンおよびホタテガイによる下痢性貝毒の蓄積機構

此木敬一, 古用幸愛, 岡田華弥, 小野田竜也, 小濱真実, 松浦宏樹, 長由扶子, 渡邊龍一, 加賀新之助, 鈴木敏之, 山下まり

第56回天然有機化合物討論会講演要旨集　56　453-457　2014/09/22

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権威ある学会の要旨集で、論文に匹敵する内容が収められている。
Synthesis and Biological Activity of the C ' D ' E ' F ' Ring System of Maitotoxin Peer-reviewed

Masahiro Kunitake, Takahiro Oshima, Keiichi Konoki, Makoto Ebine, Kohei Torikai, Michio Murata, Tohru Oishi

JOURNAL OF ORGANIC CHEMISTRY　79　(11)　4948-4962　2014/06

DOI： 10.1021/jo5005235 　

ISSN： 0022-3263
Isolation of 6-Deoxytetrodotoxin from the Pufferfish, Takifugu pardalis, and a Comparison of the Effects of the C-6 and C-11 Hydroxy Groups of Tetrodotoxin on Its Activity Peer-reviewed

Yuta Kudo, Julian Finn, Kohei Fukushima, Satsuki Sakugawa, Yuko Cho, Keiichi Konoki, Mari Yotsu-Yamashita

JOURNAL OF NATURAL PRODUCTS　77　(4)　1000-1004　2014/04

DOI： 10.1021/np401097n 　

ISSN： 0163-3864

eISSN： 1520-6025
Synthesis and identification of proposed biosynthetic intermediates of saxitoxin in the cyanobacterium Anabaena circinalis (TA04) and the dinoflagellate Alexandrium tamarense (Axat-2) Peer-reviewed

Shigeki Tsuchiya, Yuko Cho, Keiichi Konoki, Kazuo Nagasawa, Yasukatsu Oshima, Mari Yotsu-Yamashita

ORGANIC & BIOMOLECULAR CHEMISTRY　12　(19)　3016-3020　2014

DOI： 10.1039/c4ob00071d 　

ISSN： 1477-0520

eISSN： 1477-0539
The binding of okadaic acid analogues to recombinant OABP2.1 originally isolated from the marine sponge Halichondria okadai. Peer-reviewed

Konoki K, Onoda T, Furumochi S, Cho Y, Yotsu-Yamashita M, Yasumoto T

Bioorg. Med. Chem. Lett.　23　5833-5835　2013/09/06

DOI： 10.1016/j.bmcl.2013.08.0992 　
First Identification of 5,11-Dideoxytetrodotoxin in Marine Animals, and Characterization of Major Fragment Ions of Tetrodotoxin and Its Analogs by High Resolution ESI-MS/MS Peer-reviewed

Mari Yotsu-Yamashita, Yuka Abe, Yuta Kudo, Raphael Ritson-Williams, Valerie J. Paul, Keiichi Konoki, Yuko Cho, Masaatsu Adachi, Takuya Imazu, Toshio Nishikawa, Minoru Isobe

MARINE DRUGS　11　(8)　2799-2813　2013/08

DOI： 10.3390/md11082799 　

ISSN： 1660-3397
Concise synthesis and biological assessment of (+)-neopeltolide and a 16-member stereoisomer library of 8,9-dehydroneopeltolide: Identification of pharmacophoric elements Peer-reviewed

Haruhiko Fuwa, Masato Kawakami, Kenkichi Noto, Takashi Muto, Yuto Suga, Keiichi Konoki, Mari Yotsu-Yamashita, Makoto Sasaki

Chemistry - A European Journal　19　(25)　8100-8110　2013/06/17

DOI： 10.1002/chem.201300664 　

ISSN： 0947-6539 1521-3765
In Vitro Acylation of Okadaic Acid in the Presence of Various Bivalves' Extracts Peer-reviewed

Keiichi Konoki, Tatsuya Onoda, Ryuichi Watanabe, Yuko Cho, Shinnosuke Kaga, Toshiyuki Suzuki, Mari Yotsu-Yamashita

MARINE DRUGS　11　(2)　300-315　2013/02

DOI： 10.3390/md11020300 　

ISSN： 1660-3397
Isolation and Structural Determination of Two Novel Phlorotannins from the Brown Alga Ecklonia kurome Okamura, and Their Radical Scavenging Activities Peer-reviewed

Mari Yotsu-Yamashita, Sawako Kondo, Shinya Segawa, Yi-Chin Lin, Haruhiko Toyohara, Hisatomi Ito, Keiichi Konoki, Yuko Cho, Takafumi Uchida

MARINE DRUGS　11　(1)　165-183　2013/01

DOI： 10.3390/md11010165 　

ISSN： 1660-3397
Synthesis of putative biosynthetic intermediates in early stage for paralytic shellfish toxins, and their identification in toxin producing microorganisms

Shigeki Tsuchiya, Yuko Cho, Keiichi Konoki, Kazuo Nagasawa, Yasukatsu Oshima, Mari Yotsu-Yamashita

54th Symposium on The Chemistry of Natural Products　54　(54)　459-464　2012/09/01
Publisher: Symposium on the chemistry of natural products
DOI： 10.24496/tennenyuki.54.0_459 　

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The putative biosynthetic pathways for paralytic shellfish toxins (PSTs) in cyanobacteria and dinoflagellates have been recently reported based on the corresponding gene clusters and genes required for saxitoxin synthesis found by Neilan and Jakobsen et al. We chemically synthesized some intermediates predicted in early stage in biosynthesis of PSTs, and attempted to identify them in the PSTs producing cyanobacteria, Anabaena circinalis, and dinoflagellates, Alexandrium tamarense, and also in a non-toxic strains of them using LC/MS. The arginine derivative bearing an ethyl ketone moiety, which was predicted as the first intermediate of PSTs biosynthesis, was detected in both of toxic strains of A. circinalis and A. tamarense. Analytical results for other intermediates will be also presented.
Artificial ladder-shaped polyethers that inhibit maitotoxin-induced Ca2+ influx in rat glioma C6 cells Peer-reviewed

Tohru Oishi, Keiichi Konoki, Rie Tamate, Kohei Torikai, Futoshi Hasegawa, Nobuaki Matsumori, Michio Murata

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS　22　(11)　3619-3622　2012/06

DOI： 10.1016/j.bmcl.2012.04.053 　

ISSN： 0960-894X
Isolation and Structural Determination of the First 8-epi-type Tetrodotoxin Analogs from the Newt, Cynops ensicauda popei, and Comparison of Tetrodotoxin Analogs Profiles of This Newt and the Puffer Fish, Fugu poecilonotus Peer-reviewed

Yuta Kudo, Takeshi Yasumoto, Keiichi Konoki, Yuko Cho, Mari Yotsu-Yamashita

MARINE DRUGS　10　(3)　655-667　2012/03

DOI： 10.3390/md10030655 　

ISSN： 1660-3397
Identification of novel oxidized levuglandin D-2 in marine red alga and mouse tissue Peer-reviewed

Yoshikazu Kanai, Sadahiko Hiroki, Hiroyuki Koshino, Keiichi Konoki, Yuko Cho, Mirriam Cayme, Yasuo Fukuyo, Mari Yotsu-Yamashita

JOURNAL OF LIPID RESEARCH　52　(12)　2245-2254　2011/12

DOI： 10.1194/jlr.M017053 　

ISSN： 0022-2275
Lysine proximity significantly affects glycation of lysine-containing collagen model peptides Peer-reviewed

Asuka Kitamura, Kouta Matsui, Keiichi Konoki, Nobuaki Matsumori, Michio Murata, Toru Kawakami, Saburo Aimoto

BIOORGANIC & MEDICINAL CHEMISTRY　19　(7)　2125-2129　2011/04

DOI： 10.1016/j.bmc.2011.02.048 　

ISSN： 0968-0896
Optimization of simultaneous analysis of tetrodotoxin, 4-epitetrodotoxin, 4,9-anhydrotetrodotoxin, and 5,6,11-trideoxytetrodotoxin by hydrophilic interaction liquid chromatography-tandem mass spectrometry Peer-reviewed

Mari Yotsu-Yamashita, Jun-Ho Jang, Yuko Cho, Keiichi Konoki

FORENSIC TOXICOLOGY　29　(1)　61-64　2011/01

DOI： 10.1007/s11419-010-0106-x 　

ISSN： 1860-8965
Optimization of simultaneous analysis of tetrodotoxin, 4-epitetrodotoxin, 4,9-anhydrotetrodotoxin, and 5,6,11-trideoxytetrodotoxin by hydrophilic interaction liquid chromatography-tandem mass spectrometry Peer-reviewed

Mari Yotsu-Yamashita, Jun-Ho Jang, Yuko Cho, Keiichi Konoki

FORENSIC TOXICOLOGY　29　(1)　61-64　2011/01

DOI： 10.1007/s11419-010-0106-x 　

ISSN： 1860-8965
Binding of diarrheic shellfish poisoning toxins to okadaic acid binding proteins purified from the sponge Halichondria okadai Peer-reviewed

Keiichi Konoki, Kaori Saito, Hiroki Matsuura, Naoyuki Sugiyama, Yuko Cho, Mari Yotsu-Yamashita, Kazuo Tachibana

BIOORGANIC & MEDICINAL CHEMISTRY　18　(21)　7607-7610　2010/11

DOI： 10.1016/j.bmc.2010.08.043 　

ISSN： 0968-0896
Detection of Rap1A as a yessotoxin binding protein from blood cell membranes Peer-reviewed

Satoru Ujihara, Tohru Oishi, Ryota Mouri, Rie Tamate, Keiichi Konoki, Nobuaki Matsumori, Michio Murata, Yasukatsu Oshima, Naoyuki Sugiyama, Masaru Tomita, Yasushi Ishihama

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS　20　(22)　6443-6446　2010/11

DOI： 10.1016/j.bmcl.2010.09.080 　

ISSN： 0960-894X

eISSN： 1464-3405
beta-Adrenergic-regulated phosphorylation of the skeletal muscle Ca(V)1.1 channel in the fight-or-flight response Peer-reviewed

Michelle A. Emrick, Martin Sadilek, Keiichi Konoki, William A. Catterall

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　107　(43)　18712-18717　2010/10

DOI： 10.1073/pnas.1012384107 　

ISSN： 0027-8424
Physiological roles of okadaic acid in the sponge Halichondria okadai

Keiichi Konoki, Hiroki Matsuura, Kaori Saito, Yuko Cho, Tomofumi Miyamoto, Naoyuki Sugiyama, Seketsu Fukuzawa, Kazuo Tachibana

Symposium Papers for 52nd Symposium on The Chemistry of Natural Products　52　(52)　571-576　2010/09/01
Publisher: Symposium on the chemistry of natural products
DOI： 10.24496/tennenyuki.52.0_571 　

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Okadaic acid (OA) as well as dinophysistoxin-1 (DTX1) has been causative for diarrheic shellfish poisoning. Biochemical experiments were carried out to investigate interactions of the two toxins with novel okadaic acid binding proteins 2.1 (OABP2.1) and 2.3 (OABP2.3), originally isolated from the marine sponge Halichondria okadai. Firstly, the recombinant proteins for OABPs 2.1 and 2.3 were expressed in Escherichia coli BL21 (DE3) cells. Binding assays using [24-^3H]OA demonstrated that the dissociation constants K_d for the recombinant OABPs 2.1 and 2.3 were determined as 1.30±0.56 nM and 1.54±0.35 nM, respectively. Binding of [24-^3H]OA to recombinant OABP2.1 was almost equally replaced with OA and DTX1. OA-induced cytotoxicity to mouse leukemia P388 cells was inhibited by the recombinant OABPs 2.1 and 2.3 in a comparable manner. These results suggest that regulation of OA-induced toxocity by OABPs 2.1 and 2.3 may be important for symbiotic relationship present in the sponge H. okadai.
Lysine proximity significantly affects glycation of lysine-containing collagen model peptides Peer-reviewed

Asuka Kitamura, Kouta Matsui, Keiichi Konoki, Nobuaki Matsumori, Michio Murata, Toru Kawakami, Saburo Aimoto

Bioorganic and Medicinal Chemistry　19　(7)　2125-2129　2010

DOI： 10.1016/j.bmc.2011.02.048 　
Preparation of Protein and Biotin Conjugates of Tetrodotoxin and Their Biochemical Application

Yotsu-Yamashita Mari, Kaneko Riku, Yamada Kyohei, Yamaguchi Hideki, Konoki Keiichi

Symposium on the Chemistry of Natural Products, symposium papers　(51)　653-658　2009/09/01
Publisher: Symposium on the chemistry of natural products
DOI： 10.24496/tennenyuki.51.0_653 　

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Protein conjugates and biotin conjugates of tetrodotoxin (TTX) were prepared by reductive amination between 11-oxoTTX and bydrazides. The mixture of 11-oxoTTX and its 4,9-anhydro derivative (ratio 2:5) was obtained from TTX by Pfitzner-Moffatt oxidation as previously reported by Lazdunski et al. We optimized this reaction, and obtained them reproductively in approximately 60% yield. By analysis using MALDI-TOF MS, four molecules of TTX were suggested to be conjugated to one molecule of BSA (bovine serum albumin). TTX was biotylated by using biotin PEG_4 hydrazide and another biotin hydrazide reagent which has an alkyl linker between biotin and hydrazide. The inhibitory activity of this TTX-biotin conjugate to sodium channels in Neuro2A cell line was estimated approximately 1/100 of that of TTX by the preliminary result.
Total Synthesis of (+)-Decarbamoylsaxitoxin and (+)-Gonyautoxin 3 on Developed Synthetic Method

Iwamoto Osamu, Shinohara Ryoko, Konoki Keiichi, Yotsu-Yamashita Mari, Nagasawa Kazuo

Symposium on the Chemistry of Natural Products, symposium papers　(51)　181-186　2009/09/01
Publisher: Symposium on the chemistry of natural products
DOI： 10.24496/tennenyuki.51.0_181 　

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Saxitoxin (STX) (2) and its analogues known as causative agents of paralytic shellfish poisoning, so called PSP, are potent neurotoxins produced by harmful dinoflagellates. This fatal intoxication is attributed to STXs' potent affinity against the voltage gated sodium channels (NaChs), thus the toxins strongly block the influx of sodium ion and inhibit the depolarization process of neuronal cells. We have recently accomplished total synthesis of (-) and (+)-doSTX (ent-2 and 2) and (+)-STX (1) by the use of 1,3-dipolar cycloaddition reaction and unique IBX oxidation reaction. In this paper, we described the NaCh inhibitory activity of novel synthetic STX derivatives 19-22. We also succeeded in developing the new synthetic methodology for constructing the cyclic guanidine skeleton under the extremely mild conditions, which successfully allow us to the total synthesis of (+)-dcSTX (3) and (+)-GTX3 (7) from "protected" saxitoxinol 34.
Amphotericin B-induced ion flux is markedly attenuated in phosphatidylglycerol membrane as evidenced by a newly devised fluorometric method Peer-reviewed

Tetsuro Takano, Keiichi Konoki, Nobuaki Matsumori, Michio Murata

BIOORGANIC & MEDICINAL CHEMISTRY　17　(17)　6301-6304　2009/09

DOI： 10.1016/j.bmc.2009.07.036 　

ISSN： 0968-0896
MAITOTOXIN-PHOTOACTIVE PROBE BINDS TO MEMBRANE PROTEINS IN BLOOD CELLS Invited Peer-reviewed

Keiichi Konoki, Masaki Hashimoto, Kaori Honda, Kazuo Tachibana, Rie Tamate, Futoshi Hasegawa, Tohru Oishi, Michio Murata

HETEROCYCLES　79　1007-1017　2009/04

DOI： 10.3987/COM-08-S(D)78 　

ISSN： 0385-5414
Design, Synthesis, and Biological Evaluation of Fluorinated Analogues of Salicylihalamide Peer-reviewed

Yoshinori Sugimoto, Keiichi Konoki, Michio Murata, Masafumi Matsushita, Hiroshi Kanazawa, Tohru Oishi

JOURNAL OF MEDICINAL CHEMISTRY　52　(3)　798-806　2009/02

DOI： 10.1021/jm801265e 　

ISSN： 0022-2623

eISSN： 1520-4804
Total Synthesis and Biological Evaluation of (+)-Neopeltolide and Its Analogues Peer-reviewed

Haruhiko Fuwa, Asami Saito, Shinya Naito, Keiichi Konoki, Mari Yotsu-Yamashita, Makoto Sasaki

CHEMISTRY-A EUROPEAN JOURNAL　15　(46)　12807-12818　2009

DOI： 10.1002/chem.200901675 　

ISSN： 0947-6539
Interaction of ladder-shaped polyethers with transmembrane alpha-helix of glycophorin A as evidenced by saturation transfer difference NMR and surface plasmon resonance

Satoru Ujihara, Tohru Oishi, Kohei Torikai, Keiichi Konoki, Nobuaki Matsumori, Michio Murata, Yasukatsu Oshima, Saburo Aimoto

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS　18　(23)　6115-6118　2008/12

DOI： 10.1016/j.bmcl.2008.10.020 　

ISSN： 0960-894X
Convergent synthesis and biological activity of the WXYZA'B'C' ring system of maitotoxin Peer-reviewed

Tohru Oishi, Futoshi Hasegawa, Kohei Torikai, Keiichi Konoki, Nobuaki Matsumori, Michio Murata

ORGANIC LETTERS　10　(16)　3599-3602　2008/08

DOI： 10.1021/ol801369g 　

ISSN： 1523-7060
Design and synthesis of ladder-shaped tetracyclic, heptacyclic, and decacyclic ethers and evaluation of the interaction with transmembrane proteins Peer-reviewed

Kohei Torikai, Tohru Oishi, Satoru Ujihara, Nobuaki Matsumori, Keiichi Konoki, Michio Murata, Saburo Aimoto

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY　130　(31)　10217-10226　2008/08

DOI： 10.1021/ja801576v 　

ISSN： 0002-7863
Complex formation of amphotericin B in sterol-containing membranes as evidenced by surface plasmon resonance Peer-reviewed

Ryota Mouri, Keiichi Konoki, Nobuaki Matsumori, Tohru Oishi, Michio Murata

BIOCHEMISTRY　47　(30)　7807-7815　2008/07

DOI： 10.1021/bi800334p 　

ISSN： 0006-2960
Roles of integral protein in membrane permeabilization by amphidinols Peer-reviewed

Nagy Morsy, Keiichi Konoki, Toshihiro Houdai, Nobuaki Matsumori, Tohru Oishi, Michio Murata, Saburo Aimoto

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES　1778　(6)　1453-1459　2008/06

DOI： 10.1016/j.bbamem.2008.01.018 　

ISSN： 0005-2736
Structural features of dinotlagellate toxins underlying biological activity as viewed by NMR Peer-reviewed

Michio Murata, Nobuaki Matsumori, Keiichi Konoki, Tohru Oishi

BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN　81　(3)　307-319　2008/03

DOI： 10.1246/bcsj.81.307 　

ISSN： 0009-2673

eISSN： 1348-0634
Effects of lipid constituents on membrane-permeabilizing activity of amphidinols Peer-reviewed

Nagy Morsy, Toshihiro Houdai, Keiichi Konoki, Nobuaki Matsumori, Tohru Oishi, Michio Murata

BIOORGANIC & MEDICINAL CHEMISTRY　16　(6)　3084-3090　2008/03

DOI： 10.1016/j.bmc.2007.12.029 　

ISSN： 0968-0896
Isolation and characterization of okadaic acid binding proteins from the marine sponge Halichondria okadai Peer-reviewed

Naoyuki Sugiyama, Keiichi Konoki, Kazuo Tachibana

BIOCHEMISTRY　46　(40)　11410-11420　2007/10

DOI： 10.1021/bi700490n 　

ISSN： 0006-2960
Investigation on Interaction between Ladder-Shaped Polyether Compounds and Membrane Protein

Satoru Ujihara, Kohei Torikai, Ryota Mouri, Megumi Mori, Keiichi Konoki, Nobuaki Matsumori, Tohru Oishi, Michio Murata

The Symposium Papers of the 49th Symposium on the Chemistry of Natural Products　(49)　467-472　2007/08/24
Publisher: Symposium on the chemistry of natural products
DOI： 10.24496/tennenyuki.49.0_467 　

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Ladder-shaped polyether (LSP) compounds, such as brevetoxins and ciguatoxins, are thought to interact with a common motif generally occurring in membrane proteins. In this study, to examine the above hypothesis, we assessed the interactions between polycyclic ethers and various proteins using surface plasmon resonance (SPR), SDS-PAGE and NMR experiments. SPR experiments showed that membrane proteins containing transmembrane α-helices had significant affinity for yessotoxin (YTX) and a desulfated derivative (dsYTX) with the dissociation constants of about 10-100μM, whereas water-soluble proteins and a membrane protein forming a β-sheet showed relatively weak affinity for YTX and dsYTX. These results suggest that LSPs recognize membrane proteins, particularly transmembrane α-helix. Then, we examined the influence of molecular length of LSP on the affinity using SPR and SDS-PAGE. In order to specifically observe the effects of molecular length, artificial mono, tetra, hepta and deca cyclic ether (ALPs 1, 4, 7 and 10a) were synthesized and used in the experiments. The results thus obtained revealed that the affinity to transmembrane α-helix increases with increasing molecular length. In addition, decacyclic ALP10b that has four hydroxyl groups on both molecular termini was found to precipitate some membrane proteins, which may be due to specific intermolecular recognitions unique to ALP10b.
Mya arenaria Inhabiting in the Eastern Coast of Canada Acquired a Defense Mechanism against Annual Paralytic Shellfish Poisoning

V. Monica Bricelj, Laurie Connell, 此木敬一, Scott P. MacQuarrie, Todd Scheuer, William A. Catterall, Vera L. Trainer

The Proceedings of the 48th Natural Product Chemistry Symsposium　(48)　49-54　2006/09
Publisher: Symposium on the chemistry of natural products
DOI： 10.24496/tennenyuki.48.0_49 　

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Paralytic shellfish poisoning (PSP) toxins such as Saxitoxin (STX) cause human fatalities by blocking Na^+ conductance in nerve fibers. Bivalve molluscs, the primary vectors of PSP in humans, show marked inter-species variation in their capacity to accumulate PSP toxins. Here we demonstrate that there is also inter-population variation in PSP resistance within a species. Softshell clam Mya arenaria were collected from two areas. One of them is subject to recurrent annual toxic blooms of Alexandrium spp. (PSP area), and the other has never suffered PSP up to date (PSP-free area). The clams from PSP area were far more tolerant to PSP toxins than those from PSP-free area, accumulated higher amount of toxicity, and survived. The amino acid sequences of voltage-dependent Na^+ channels in the pore regions, the binding site of STX, turned out to be different by only one amino acid between PSP toxin-sensitive and resistant clams. Patch clamp recording proved the substitution made the channel about 1,500-fold less sensitive to STX. This study establishes a molecular basis for intraspecific variation in toxin resistance to PSP.
P-56 SODIUM CHANNEL MUTATION RESPONSIBLE FOR SAXITOXIN RESISTANCE IN CLAMS INCREASES RISK OF PSP

Bricelj V. Monica, Connell Laurie, Konoki Keiichi, MacQuarrie Scott P., Scheuer Todd, Catterall William A., Trainer Vera L.

International Symposium on the Chemistry of Natural Products　2006　"P-56"　2006/07/23
Publisher: Symposium on the chemistry of natural products
DOI： 10.24496/intnaturalprod.2006.0__P-56_ 　
Sites of proteolytic processing and noncovalent association of the distal C-terminal domain of Cav1.1 channels in skeletal muscle Peer-reviewed

JT Hulme, K Konoki, TWC Lin, MA Gritsenko, DG Camp, DJ Bigelow, WA Catterall

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　102　(14)　5274-5279　2005/04

DOI： 10.1073/pnas.0409885102 　

ISSN： 0027-8424
Sodium channel mutation leading to saxitoxin resistance in clams increases risk of PSP Peer-reviewed

VM Bricelj, L Connell, K Konoki, SP MacQuarrie, T Scheuer, WA Catterall, VL Trainer

NATURE　434　(7034)　763-767　2005/04

DOI： 10.1038/nature03415 　

ISSN： 0028-0836
Development of biotin-avidin technology to investigate okadaic acid-promoted cell signaling pathway Invited Peer-reviewed

K Konoki, N Sugiyama, M Murata, K Tachibana, Y Hatanaka

TETRAHEDRON　56　(46)　9003-9014　2000/11

DOI： 10.1016/S0040-4020(00)00752-3 　

ISSN： 0040-4020
Maitotoxin-induced calcium influx in erythrocyte ghosts and rat glioma C6 cells, and blockade by gangliosides and other membrane lipids Peer-reviewed

K Konoki, M Hashimoto, M Murata, K Tachibana

CHEMICAL RESEARCH IN TOXICOLOGY　12　(10)　993-1001　1999/10

DOI： 10.1021/tx990014m 　

ISSN： 0893-228X
Direct observation of binding between biotinylated okadaic acids and protein phosphatase 2A monitored by surface plasmon resonance Peer-reviewed

K Konoki, N Sugiyama, M Murata, K Tachibana

TETRAHEDRON LETTERS　40　(5)　887-890　1999/01

DOI： 10.1016/S0040-4039(98)02474-5 　

ISSN： 0040-4039
Inhibition of maitotoxin-induced Ca2+ influx in rat glioma C6 cells by brevetoxins and synthetic fragments of maitotoxin Peer-reviewed

K Konoki, M Hashimoto, T Nonomura, M Sasaki, M Murata, K Tachibana

JOURNAL OF NEUROCHEMISTRY　70　(1)　409-416　1998/01

DOI： 10.1046/j.1471-4159 　

ISSN： 0022-3042
Studies on Action Mechanism of Calcium Influx Elicited by Maitotoxin, the Most Toxic Marine Natural Product Peer-reviewed

Keiichi Konoki

Ph.D. Thesis, Graduate School of Science, The University of Tokyo　1997/03/10

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学位論文
Chemical structures of amphidinols 5 and 6 isolated from marine dinoflagellate Amphidinium klebsii and their cholesterol-dependent membrane disruption Peer-reviewed

GK Paul, N Matsumori, K Konoki, M Murata, K Tachibana

JOURNAL OF MARINE BIOTECHNOLOGY　5　(2-3)　124-128　1997

ISSN： 0941-2905
Blockade of MTX-induced Ca2+ influx in rat glioma C6 cells by alkylamines Peer-reviewed

K Konoki, M Hashimoto, M Murata, K Tachibana, T Yasumoto

JOURNAL OF NATURAL TOXINS　5　(2)　209-217　1996/06

ISSN： 1058-8108
Structure of amphidinol 3 and its cholesterol-independent membrane perturbation: A strong antifungal metabolites produced by dinoflagellate Amphidinium klebsii．

Gopal Krishina Paul, Nobuaki Matsumori, Keiichi Konoki, Michio Murata, Kazuo Tachibana

Harmful and Toxic Algal Blooms　503-506　1996

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Intergovernmental Oceanographic Commision of UNESCO
Cholesterol-independent membrane disruption caused by triterpenoid saponins Peer-reviewed

M Hu, K Konoki, K Tachibana

BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM　1299　(2)　252-258　1996/01

ISSN： 0005-2760
MEMBRANE PERTURBATION OF PARDAXINS, DEFENSIVE PEPTIDES OF FLATFISH

K KONOKI, M SASAKI, K TACHIBANA

PEPTIDE CHEMISTRY 1992　402-405　1993
Toxins produced by organisms in nature Peer-reviewed

Mari Yotsu-Yamashita, Keiichi Konoki, Hidetoshi Inagaki, Naoki Mori, Akira Mori

Show all ︎Show first 5

Misc. 48

無毒のサキシトキシン鏡像異性体標準物質の開発

渡邊龍一, 高柳優夏, 千葉修, 石塚颯, 小田木陽, 小澤眞由, 沼野聡, 内田肇, 松嶋良次, 此木敬一, 山下まり, 長澤和夫, 鈴木敏之

日本食品衛生学会学術講演会講演要旨集　119th　2023
フグ毒テトロドトキシンの生合成経路の推定

山下まり, 工藤雄大, 工藤雄大, 上山望, HANIFIN Charles T., 沼野聡, 長由扶子, 此木敬一

日本水産学会大会講演要旨集(CD-ROM)　2022　2022
Screening for metabolites of paralytic shellfish toxins in the scallop, Patinopecten yessoensis.

沼野聡, 沼野聡, 工藤雄大, 工藤雄大, 長由扶子, 此木敬一, 山下まり

日本農芸化学会大会講演要旨集(Web)　2021　2021

ISSN： 2186-7976
Synthetic Study of the W-F’ Ring Segment of Maitotoxin

梅野圭太郎, 尾上久晃, 此木敬一, 鳥飼浩平, 保野陽子, 大石徹

日本化学会春季年会講演予稿集(Web)　101st　2021
生合成酵素を用いたドウモイ酸類縁体の調製と構造活性相関

前野優香理, 小瀧裕一, 寺田竜太, 日高將文, 長由扶子, 此木敬一, 山下まり

日本農芸化学会東北支部大会プログラム・講演要旨集　156th (CD-ROM)　2021
テトロドトキシン推定生合成中間体のテトロドトキシン含有生物への投与

杉本敬太, 工藤雄大, 宮坂忠親, 安立昌篤, 長由扶子, 此木敬一, 千葉親文, 西川俊夫, 山下まり

日本農芸化学会大会講演要旨集(Web)　2019　2019

ISSN： 2186-7976
東日本で養殖したホタテガイ中のLC-MS/MSによる麻痺性貝毒分析

沼野聡, 工藤雄大, 長由扶子, 此木敬一, 山下まり

日本農芸化学会大会講演要旨集(Web)　2019　2019

ISSN： 2186-7976
ソロモン諸島産の海洋生物中のNav阻害活性物質の探索

春日政人, PUILINGI Clyde Gorapava, 角替俊輔, 中崎敦夫, 長由扶子, 西川俊夫, 此木敬一, 山下まり

日本農芸化学会大会講演要旨集(Web)　2019　2019

ISSN： 2186-7976
マイトトキシンの膜透過性亢進作用の機構解明に向けた電気生理学的アプローチ

山田智士, 岩本真幸, 長由扶子, 老木成稔, 村田道雄, 山下まり, 此木敬一

日本農芸化学会東北支部大会プログラム・講演要旨集　153rd　82　2018/09/22
ホタテガイ中腸腺に存在するオカダ酸アシル化酵素の探索法の開発

寺内将斗, 古用幸愛, 長由扶子, 山下まり, 此木敬一

日本農芸化学会東北支部大会プログラム・講演要旨集　153rd　82　2018/09/22
記憶喪失性貝毒ドウモイ酸の新規生合成中間体の同定と生合成経路の解明

前野優香理, 小瀧裕一, 寺田竜太, 長由扶子, 此木敬一, 山下まり

トキシンシンポジウム予稿集　65th　31‐32　2018/06/28

ISSN： 1344-9346
紅藻ハナヤナギ(Chondria armata)から同定したドウモイ酸の推定生合成中間体のLC‐MS分析法の検討

前野優香理, 山下まり, 長由扶子, 此木敬一, 小瀧裕一, 寺田竜太

日本水産学会大会講演要旨集　2018　106　2018/03/26
¹⁵N同位体標識培地による渦鞭毛藻の麻痺性貝毒及び生合成中間体への¹⁵N取り込み挙動の解析

長由扶子, 土屋成輝, 此木敬一, 大島泰克, 山下まり

日本水産学会大会講演要旨集　2018　106　2018/03/26
記憶喪失性貝毒ドウモイ酸の生合成経路に関する研究

前野優香理, 小瀧裕一, 長由扶子, 此木敬一, 山下まり

日本農芸化学会大会講演要旨集(Web)　2018　ROMBUNNO.2A18a12 (WEB ONLY)　2018/03/05

ISSN： 2186-7976
海洋生物における新規テトロドトキシン関連化合物の探索

上山望, 杉本敬太, 長由扶子, 此木敬一, 山下まり

日本農芸化学会大会講演要旨集(Web)　2018　ROMBUNNO.2A18a11 (WEB ONLY)　2018/03/05

ISSN： 2186-7976
クロイソカイメン共生菌が生産する新規有毒二次代謝産物の構造決定

菊池颯, 岡田華弥, 長由扶子, 吉田慎一朗, KWON Eunsang, 山下まり, 此木敬一

日本農芸化学会大会講演要旨集(Web)　2018　ROMBUNNO.3A18a14 (WEB ONLY)　2018/03/05

ISSN： 2186-7976
Inhibition of Voltage-gated Sodium Channel Subtypes (Na_v1.1-Na_v1.7) by Tetrodotoxin Analogues

塚本匡顕, 千葉雪絵, 若森実, 日高將文, 山田智士, 角替俊輔, 長由扶子, 榊原良, 今津拓也, 所聖太, 佐竹佳樹, 安立昌篤, 西川俊夫, 山下まり, 此木敬一

天然有機化合物討論会講演要旨集(Web)　60th　2018

ISSN： 2433-1856
神経毒とNeuroscience 毒性のメカニズムと症候貝類,魚類,腔腸動物の毒

山下まり, 此木敬一

Clinical Neuroscience　35　(12)　1443‐1448　2017/12/01

ISSN： 0289-0585
フグ由来のテトロドトキシン関連化合物の合成

杉本敬太, 上山望, 長由扶子, 此木敬一, 西川俊夫, 山下まり

日本農芸化学会東北支部大会プログラム・講演要旨集　152nd　12　2017/11/01
ベラトリジンによる電位依存性ナトリウムチャネルの不活性化遅延作用に対するクランベシンB類縁体の抑制効果

塚本匡顕, 千葉雪絵, 中崎敦夫, 石川裕生, 中根嘉祈, 長由扶子, 山下まり, 西川俊夫, 此木敬一

日本農芸化学会大会講演要旨集(Web)　2017　2017

ISSN： 2186-7976
電位依存性ナトリウムチャネルのサブタイプを識別するテトロドトキシン類縁体の探索

千葉雪絵, 塚本匡顕, 長由扶子, 安立昌篤, 榊原良, 所聖太, 中崎敦夫, 石川裕生, 西川俊夫, 山下まり, 此木敬一

日本農芸化学会大会講演要旨集(Web)　2015　2015

ISSN： 2186-7976
電位依存性ナトリウムチャネルに対するテトロドトキシンおよび類縁体の活性阻害評価

塚本匡顕, 千葉雪絵, 長由扶子, 安立昌篤, 榊原良, 所聖太, 今津拓也, 中崎敦夫, 石川裕生, 西川俊夫, 山下まり, 此木敬一

日本農芸化学会東北支部大会プログラム・講演要旨集　150th　2015
日本農芸化学会大会学会見聞録

大坪嘉行, 此木敬一, 榎本賢, 松沢智彦, 永塚貴弘, 都築毅, 戸部隆太, 渡部昭, 小酒井貴晴, 岡澤敦司

バイオサイエンスとインダストリー　75　(4)　331-340　2014/07/10
Publisher: バイオサイエンスインダストリー協会

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ISSN 0914-8981
日本農芸化学会大会学会見聞録

大坪先生, 此木敬一, 後藤先生, 新谷先生, 米山先生, 木村先生, 井上先生, 二井先生

バイオサイエンスとインダストリー　2014/07
Publisher: バイオサイエンスインダストリー協会
The First Identification of the Novel Tetrodotoxin Analog, 6-Deoxytetrodotoxin, and its Biological Activity

Y. Kudo, K. Konoki, Y. Cho, M. Yotsu-Yamashita

PLANTA MEDICA　79　(10)　846-847　2013/07

ISSN： 0032-0943

eISSN： 1439-0221
P-33 Isolation and Structural Determination of New Analogs of Tetrodotoxin from Okinawan Newt Cynops ensicauda popei(Poster Presentation)

Kudo Yuta, Konoki Keiichi, Cho Yuko, Yasumoto Takeshi, Yotsu-Yamashita Mari

Symposium on the Chemistry of Natural Products, symposium papers　53　(0)　367-372　2011
Publisher: Symposium on the Chemistry of Natural Products Steering Committee
DOI： 10.24496/tennenyuki.53.0_367 　

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Tetrodotoxin (TTX) is distributed in wide range of animals, marine puffer fish and terrestrial newts and frogs, for examples. We have isolated various TTX analogs from these animals, and attempted to obtain clues to biosynthetic pathway of TTX from the structures of these analogs. Here we isolated four new analogs of TTX from the Okinawan newt Cynops ensicauda popei, and determined their structures as 8-epi-5,6,11-trideoxyTTX, its 4,9-anhydro derivative, its 1-hydroxy derivative, and its 1-hydroxy-4,4a-anhydro derivative, by spectroscopic method. These analogs are not detected in puffer fish, instead, 5,6,11-trideoxyTTX is detected as a major analog in puffer fish eggs. 1-Hydroxy type analog might be specific to newts, since 1-hydroxy-5,11-dideoxyTTX was previously isolated from the other species of newt, Taricha granulosa, by other group. This is the first identification of 4,4a-anhydro type analog of TTX from the natural source.
日本農芸化学会大会学会見聞録

七谷圭, 新谷尚弘, 後藤知子, 白川仁, 都築毅, 榎本賢, 此木敬一, 小関卓也, 日出間志寿, 稲葉靖子, 宮内啓介, 矢部富雄

バイオサイエンスとインダストリー　68　(4)　263-264　2010/07
Publisher: 一般財団法人バイオインダストリー協会
農芸化学会大会

七谷圭, 新谷尚弘, 後藤知子, 白川仁, 都築毅, 榎本賢, 此木敬一, 小関卓也, 日出間志寿, 稲葉靖子, 宮内啓介, 矢部富雄

バイオサイエンスとインダストリー = Bioscience & industry　68　(4)　259-268　2010/07/01
Publisher: バイオインダストリー協会
ISSN： 0914-8981
Mystery of organism storing poisonous secondary metabolite. Discovery of Halichondria okadai-derived novel okadaic acid-biding protein

Keiichi Konoki

化学と生物　47　(6)　376-378　2009/06/01
Publisher: 学会出版センター
DOI： 10.1271/kagakutoseibutsu.47.376 　
有毒二次代謝産物を貯蔵する生物の謎 : クロイソカイメン由来の新規オカダ酸結合タンパク質の発見

此木敬一

化学と生物　47　(6)　376-378　2009/06/01
Publisher: 公益社団法人日本農芸化学会
DOI： 10.1271/kagakutoseibutsu.47.376 　

ISSN： 0453-073X
Screening of proteins for interaction with ladder-shaped polyethers by polymer-supported ligand

氏原悟, 毛利良太, 此木敬一, 松森信明, 大石徹, 村田道雄, 杉山直幸, 石濱泰, 冨田勝

日本化学会講演予稿集　89th　(2)　1376　2009/03/13

ISSN： 0285-7626
P-50 Total Synthesis of (+)-Saxitoxin and Evaluation of Na^+ Channel Inhibitory Activity of STX Derivatives(Poster Presentation)

Iwamoto Osamu, Konoki Keiichi, Yotsu-Yamashita Mari, Nagasawa Kazuo

Symposium on the Chemistry of Natural Products, symposium papers　50　(0)　689-694　2008
Publisher: Symposium on the Chemistry of Natural Products Steering Committee
DOI： 10.24496/tennenyuki.50.0_689 　

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Saxitoxin (STX) (1) and its derivatives are known to be neurotoxins that block the voltage-gated sodium channels, which are critical for depolarization and conduction in most excitable cells. STX (1) also binds to other receptor proteins, such as calcium and potassium channels, and appears to be of considerable biological importance. We have recently achieved an enantioselective total synthesis of (-)-doSTX (2). Herein, we described an enantioselective total synthesis of (+)-STX (1) with an improved synthetic method. Our synthesis of (-)-doSTX (2) features direct oxidation with o-iodoxybenzoic acid (IBX) at the α-position of the β-amino-substituted ketone, which was synthesized based upon the 1,3-dipolar cycloaddition reaction between methyl crotonate (6) and the chiral nitrone 5. In this synthetic study, we used the nitro-olefin 12 as a dipolarophile instead of the corresponding α,β-unsaturated ester to simplify the introduction of C5-nitrogene group. The 1,3-dipolar cycloaddition reaction of chiral nitrone ent-5 and nitro-olefin 17 gave 5-nitro-isoxazolidine 18 quantitatively. The chemoselective reduction of NO_2 group to NH-OH at C5 in the presence of N-O bond in the isoxazolidine ring was succeeded by treatment with Zn-AcOH condition. The nitrogen atom in NH-OH group of 21 was then protected with Cbz group, followed by reduction of two N-O bonds using TiCl_3 and Zn gave 2,3-diamino-1-alcohol 26. After several conversions, 13-carbamoyl-guanidinealcohol 37 was in hand. The completion of a formal total synthesis of (+)-STX (1) was achieved by treatment of 37 with B(OCOCF_3)_3 and gave β-saxitoxinol (38) in total 14 steps 4.5% yield.
7 Design and Synthesis of Ladder-Shaped Polyethers for Exploring Interaction with Transmembrane Proteins(Oral Presentation)

Oishi Tohru, Aimoto Saburo, Torikai Kohei, Hasegawa Futoshi, Ujihara Satoru, Mouri Ryouta, Tamate Rie, Konoki Keiichi, Matsumori Nobuaki, Murata Michio

Symposium on the Chemistry of Natural Products, symposium papers　50　(0)　65-70　2008
Publisher: Symposium on the Chemistry of Natural Products Steering Committee
DOI： 10.24496/tennenyuki.50.0_65 　

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Ladder-shaped polyether (LSP) toxins represented by brevetoxins are thought to bind to transmembrane (TM) proteins. To elucidate the interactions of LSPs with TM proteins, we have synthesized artificial ladder-shaped polyethers (ALPs) containing 6/7/6/6 tetracyclic, 6/7/6/6/7/6/6 heptacyclic, and 6/7/6/6/7/6/6/7/6/6 decacyclic system, based on the convergent method via α-cyano ethers. The ALPs possessing the simple iterative structure with different number of rings would be useful for structure-activity relationship studies on the molecular length. Two series of ALPs were prepared, (i) both sides were functionalized as diols (A series), and (ii) one side remained as diol and the other side was protected as benzyl ethers (B series), and the interaction of these ALPs with TM proteins was evaluated, based on dissociation of glycophorin A (GpA) dimers into monomers. The heptacyclic ether (ALP7B) elicited the most potent activity in the presence of 2% SDS buffer, whereas the decacyclic ether (ALP10A) exhibited intriguing phenomenon to induce precipitation of GpA in a dose-dependent manner, under the low concentration of SDS (0.03%). The different activities among the ALPs can be accounted for by the concept of 'hydrophobic matching' i.e. lengths of the hydrophobic region including the side chains of ALP7B and ALP10A are ca. 25Å, which match the lengths of the hydrophobic region of α-helical TM proteins, as well as the hydrophobic thickness of lipid bilayer membranes.
Voltage-gated ion channels and gating modifier toxins

William A. Catterall, Sandrine Cestele, Vladimir Yarov-Yarovoy, Frank H. Yu, Keiichi Konoki, Todd Scheuer

TOXICON　49　(2)　124-141　2007/02

DOI： 10.1016/j.toxicon.2006.09.022 　

ISSN： 0041-0101
P-77 Investigation on Interaction Between Ladder-Shaped Polyether Compounds and Membrane Protein

Ujihara Satoru, Torikai Kohei, Mouri Ryota, Mori Megumi, Konoki Keiichi, Matsumori Nobuaki, Oishi Tohru, Murata Michio

Symposium on the Chemistry of Natural Products, symposium papers　49　(0)　467-472　2007
Publisher: Symposium on the Chemistry of Natural Products Steering Committee
DOI： 10.24496/tennenyuki.49.0_467 　

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Ladder-shaped polyether (LSP) compounds, such as brevetoxins and ciguatoxins, are thought to interact with a common motif generally occurring in membrane proteins. In this study, to examine the above hypothesis, we assessed the interactions between polycyclic ethers and various proteins using surface plasmon resonance (SPR), SDS-PAGE and NMR experiments. SPR experiments showed that membrane proteins containing transmembrane α-helices had significant affinity for yessotoxin (YTX) and a desulfated derivative (dsYTX) with the dissociation constants of about 10-100μM, whereas water-soluble proteins and a membrane protein forming a β-sheet showed relatively weak affinity for YTX and dsYTX. These results suggest that LSPs recognize membrane proteins, particularly transmembrane α-helix. Then, we examined the influence of molecular length of LSP on the affinity using SPR and SDS-PAGE. In order to specifically observe the effects of molecular length, artificial mono, tetra, hepta and deca cyclic ether (ALPs 1, 4, 7 and 10a) were synthesized and used in the experiments. The results thus obtained revealed that the affinity to transmembrane α-helix increases with increasing molecular length. In addition, decacyclic ALP10b that has four hydroxyl groups on both molecular termini was found to precipitate some membrane proteins, which may be due to specific intermolecular recognitions unique to ALP10b.
赤潮毒蔓延域に生息するオオノガイに見つかった耐性機構

此木敬一

化学と生物　44　(10)　716-721　2006/10
Publisher: Japan Society for Bioscience, Biotechnology, and Agrochemistry
DOI： 10.1271/kagakutoseibutsu1962.44.716 　

ISSN： 0453-073X
カナダ東部麻痺性貝毒蔓延地域に生息する : オオノガイが獲得した耐性機構

此木敬一

化学と生物　44　(10)　716-721　2006/10/01
Publisher: 公益社団法人日本農芸化学会
DOI： 10.1271/kagakutoseibutsu1962.44.716 　

ISSN： 0453-073X
海外の研究室訪問(19)ワシントン大学カテラール研へようこそ!

此木敬一

化学　61　(8)　32-35　2006/08
Publisher: 化学同人
ISSN： 0451-1964
Visiting Foreign Scientific Laboratories 19 - Welcome to Catterall Lab

Keiichi Konoki

Chemistry (Monthly Periodical)　61　32-35　2006/07/18
Publisher: Kagaku-Dojin Publishing Company,INC
9 Mya arenaria Inhabiting in the Eastern Coast of Canada Acquired a Defense Mechanism against Annual Paralytic Shellfish Poisoning

Bricelj Monica V, Connell Laurie, Konoki Keiichi, MacQuarrie Scott P, Scheuer Todd, Catterall William A, Trainer Vera L

Symposium on the Chemistry of Natural Products, symposium papers　48　(0)　49-54　2006
Publisher: Symposium on the Chemistry of Natural Products Steering Committee
DOI： 10.24496/tennenyuki.48.0_49 　

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Paralytic shellfish poisoning (PSP) toxins such as Saxitoxin (STX) cause human fatalities by blocking Na^+ conductance in nerve fibers. Bivalve molluscs, the primary vectors of PSP in humans, show marked inter-species variation in their capacity to accumulate PSP toxins. Here we demonstrate that there is also inter-population variation in PSP resistance within a species. Softshell clam Mya arenaria were collected from two areas. One of them is subject to recurrent annual toxic blooms of Alexandrium spp. (PSP area), and the other has never suffered PSP up to date (PSP-free area). The clams from PSP area were far more tolerant to PSP toxins than those from PSP-free area, accumulated higher amount of toxicity, and survived. The amino acid sequences of voltage-dependent Na^+ channels in the pore regions, the binding site of STX, turned out to be different by only one amino acid between PSP toxin-sensitive and resistant clams. Patch clamp recording proved the substitution made the channel about 1,500-fold less sensitive to STX. This study establishes a molecular basis for intraspecific variation in toxin resistance to PSP.
有機化合物の標識化製造技術に関する研究--海洋ポリエーテル毒とナトリウムチャネルの相互作用の解析 (原子核をプロープとする物理・化学研究)

巻出義紘, 橘和夫, 此木敬一

原研施設利用共同研究成果報告書　(41)　8-13　2001
Publisher: 東京大学原子力研究総合センター
Chemical structure of endogenous oubain

Keiichi Konoki

Chemistry and Chemical Industry　53　(6)　706-706　2000/06
Publisher: Chemical Society of Japan
ISSN： 0022-7684
5 Okadaic Acid-Binding Proteins from the Sponge Halichondria Okadai : a Clue to the Molecular Mechanisms of Self-Resistance

Sugiyama Naoyuki, Fukatsu Katsushi, Konoki Keiichi, Murata Michio, Tachibana Kazuo

Symposium on the Chemistry of Natural Products, symposium papers　42　(0)　25-30　2000
Publisher: Symposium on the Chemistry of Natural Products Steering Committee
DOI： 10.24496/tennenyuki.42.0_25 　

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Marine sponges are known to be treasure houses of bioactive metabolites, many being cytotoxic, to natural product chemists. This arises a question why sponges are all right with strong cytotoxins. The answer could be either reduced affinity between the toxin molecule and its target cellular component, and/or existence of another binding molecule for the toxin to lessen its availability as the free form. In order to investigate such speculations, proteinaceous components in the aqueous extract of the sponge Halichondria okadai were examined in terms of binding affinity to a polyethereal cytotoxin, okadaic acid (1), because this sponge is known to contain an abundant amount of 1. After preliminary fractionation by ammonium sulfate precipitation, considerable activity, which was further enhanced by removal of 1 with acetone precipitation, was perceived using the conventional binding assay using a tritiated 1 (2) and separation between the bound and the unbound by quick gel filtration. Active fractions were further separated through ion-exchange and other chromatographic techniques as guided by the same binding assay, eventually yielding two entities with molecular sizes of ca. 37kDa (OABP1) and 25kDa (OABP2) as indicated on SDS-PAGE. Conventional sequential analyses of their endoproteinase digests and the following PCR protocol indicated OABP1 to be the catalytic subunit of protein phosphatase 2A (PP2A), the known target enzyme of 1, but with much reduced affinity than mammalian ones, while OABP2 failed to show any homology. Based on the ample amount of the latter and on its low Kd of 0.9nM, this protein is most likely involved in sequestration of 1 from its action to PP2A. A complete amino acid sequence of OABP2 was obtained by 5'- and 3'-RACE techniques. Combined with its ESI mass spectrum showing multi-charged ions, deletion of amino-terminal methionine is the only post-translational modification to result in a protein of 189 amino acid residues.
その他

井本英夫, 大西洋, 此木敬一, 朝倉清高, 大山聖子, 森澤正昭

東京大学大学院理学系研究科・理学部廣報　30　(2)　30-38　1998/09
Publisher: 東京大学大学院理学系研究科・理学部

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一日体験化学教室／臨海実験所において受精の生物学に関する国際シンポジウム開催される／東京大学名誉教授称号授与伝達式／理学系研究科長(理学部長)と理学部職員組合との交渉／人事異動報告／博士(理学)学位授与者
超活性海洋天然物マイトトキシンによるCa^<2+>流入機構の解明研究

此木敬一, 橋本雅棋, 村田道雄, 橘和夫, 安元健

日本分子生物学会年会プログラム・講演要旨集　19　378-378　1996/08/01
Synergistic Effects of Shark Repellents upon Lipid Bilayer.

川村明, 此木敬一, 橘和夫

日本化学会講演予稿集　67th　(2)　878　1994/03

ISSN： 0285-7626
20 MECHANISMS OF ACTION FOR PERMEABILIZATION OF LIPID BILAYER MEMBRANE BY DEFENSE SUBSTANCES OF SOLES PARDACHIRUS

Kawamura A, Konoki K, Onishi Y, Tachibana K

Symposium on the Chemistry of Natural Products, symposium papers　36　(0)　152-158　1994
Publisher: Symposium on the Chemistry of Natural Products Steering Committee
DOI： 10.24496/tennenyuki.36.0_152 　

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Soles of the genus Pardachirus are characterized by their chemical defense against predation with a copious and ichthyotoxic secretion being discharged upon disturbance. Two chemical classes of bioactive entities, namely, steroid monoglycosides and amphiphilic peptides, have been isolated from each secretion of two different biological species. Based on permeabilization of phospholipid bilayer exhibited by these components at the lower concentrations than their EC's for various bioactivity, their mechanisms of action may well be attributed to nonspecific derangement of animal cell membrane without binding to any particular biomolecule. In this study, an assay method of membrane permeabilization was employed, where calcein was encapsulated in unilamellar liposomes of egg-yolk phosphatidylcholine as the cellular model and its leakage outward was assessed by the increase of fluorescence, in order to evaluate (i) the function of the hydrophobic N-terminal region of pardaxin M-1, a representative peptidic component, as the membrane binding region, and (ii) the significance of the existence in the defense secretion of steroid glycosides, i.e., pavoninins and mosesins, which appear to behave in a similar manner as pardaxins in this membranal action but with lower potencies. As a result of the binding analyses with concentrations of the test sample and liposomes as two independent variants and application of Langmuir's adsorption isotherm with the two-state model to the outcomes, the N-terminal region was revealed not only to function as the strong binding region, but also to enhance when bound the deranging activity putatively of the α-helical region at the middle of the 33 amino acid sequence by the factor of 6 times. In this model assay with varied cholesterol contents in the lipid bilayer, the defensive steroid glycosides were shown to be indifferent to this membranal component in their permeabilizing action, being unlike the conventional hemolytic saponins. In addition, different kinetics exhibited here between the steroid glycosides and pardaxins implied that the former's is rather transient while the latter's is persistent with all-or-none rupture of liposomes. An extent of synergism, possibly with such differently allotted functions in the defensive action, was also shown between the two chemical entities.
サメ忌避性ウシノシタ防御分泌液の生体膜活性成分による活性発現機構

此木敬一, 佐々木誠, 橘和夫

日本化学会講演予稿集　64th　(1)　275　1992/09

ISSN： 0285-7626

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Books and Other Publications 7

第65回天然有機化合物討論会要旨集

袴田真有, 東海林千容, 石塚颯, 安達栞菜, 大澤瞳生, 廣住燎亮, 土屋成輝, 長由扶子, 工藤雄大, 此木敬一, 大島泰克, 長澤和夫, 山下まり

2023/09
月刊海洋2023年1-2月号

長由扶子, 日手間志寿, 大村卓朗, 土屋成輝, 小池一彦, 小池香苗, 及川寛, 此木敬一, 大島泰克, 山下まり

海洋出版株式会社　2023/01
月刊海洋2023年1-2月号

山下まり, 工藤雄大, 上山望, 八重樫優士, 長由扶子, 此木敬一

海洋出版株式会社　2023/01
カキ・ホタテガイの科学

尾定, 誠, 小坂善信, 田邉徹, 吉田達, 山下まり, 此木敬一, 伊藤直樹, 落合芳博, 宮澤晴彦, 高橋計介

朝倉書店　2019/08

ISBN: 9784254485035
Clinical Neuroscience

山下まり, 此木敬一

中外医学社　2017/12/01
Sorrel Organic Chemistry

Masami Ishibashi, Hideo Kigoshi, Makoto Sasaki, Michio Murata

Tokyo Kagaku Dozin CO., LTD　2009/11

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翻訳本
Marine Natural Product Chemistry

Shosuke Yamamura, Koji Hasegawa, Hideo Kigoshi

Industrial Publishing & Consulting, Inc.　2008/06/30

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担当分：第1章1.2.8，85－94頁

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Presentations 247

Inhibitory activity of the voltage-gated sodium channels by arachidonic acid, isolated from the marine sponge Halichondria okadai, and other fatty acids.

Osamu CHIBA, Noriko SHIMADA, Yuta KUDO, Yuko CHO, Mari YOTSU-YAMASHITA, Keiichi Konoki

The 2022 Annual Meeting of Japan Society for Bioscience, Biotechnology, and Agrochemistry　2022/03/17
Maitotoxin による細胞膜の Blebbing の機構解明

田端滉樹, 角替俊輔, 後藤萌香, 吉尾柊太郎, 由扶子, 村田道雄, 山下まり, 此木敬一

日本農芸化学会東北支部第156 回大会　2021/10/09
Maitotoxin による細胞膜の Blebbing の機構解明

田端滉樹, 角替俊輔, 後藤萌香, 吉尾柊太郎, 長由扶子, 村田道雄, 山下まり, 此木敬一

第156回日本農芸化学会東北支部大会　2021/10/08
オカダ酸結合タンパク質を用いる新規下痢性貝毒定量法の開発

此木敬一, 棟本健, 田端滉樹, 内田肇, 渡邊龍一, 長由扶子, 工藤雄大, 山下まり

令和７年度日本水産学会春季大会　2025/03/28
珪藻Nitzschia navis-varingica複数株のドウモイ酸生合成遺伝子の発現解析と関連物質の分析

山下まり, 芦田康洋, 望月政希, 前野優香理, Puilingi Clyde, G, ソロモン諸島国立大, 工藤雄大, 此木敬一, 長由扶子, 小瀧裕一

令和７年度日本水産学会春季大会　2025/03/28
Alexandrium catenella（Group I）有毒無毒姉妹サブクローンのサキシトキシン生合成遺伝子sxtGの比較解析

長由扶子, 大村卓朗, 此木敬一, 大島泰克, 山下まり

令和７年度日本水産学会春季大会　2025/03/28
Prediction of isoforms of saxitoxin biosynthetic enzyme, SxtG, in the toxic dinoflagellate subclone, Axat-2 of Alexandrium catenella (Group I)

○Yuko CHO, Takuo Omura, Keiichi Konoki, Yasukatsu Oshima, Mari Yotsu-Yamashita

2025/03/07
Elucidation of saxitoxin biosynthetic pathway based on the heterologous expression of its biosynthetic enzyme, SxtH

○Shiori AONUMA, Mayu HAKAMADA, Ryosuke HIROZUMI, Yuta KUDO, Yuko CHO, Keiichi KONOKI, Hayate ISHIZUKA, Kazuo NAGASAWA, Mari YOTSU-YAMASHITA

2025/03/08
Localization of tetrodotoxin and paralytic shelfish toxins in the tissues of Japanese Akazara scallop, Chlamys (Azumapecten) farreri akazara

○Ranmaru Matsui1, Yuta Kudo2,1, Yuko Cho1, Keiichi Konoki1, Mari Yotsu-Yamashita1

2025/03/08
Synthesis of saxitoxin biosynthetic intermediates for elucidation of the mechanism for formation of its tricyclic skeleton

○Ryosuke Hirozumi1, Mayu Hakamada1, Takashi Minowa1, Yuko Cho1, Yuta Kudo2,1, Keiichi Konoki1, Yasukatsu Oshima3, Kazuo Nagasawa4, Mari Yotsu-Yamashita1

2025/03/07
Rapid Identification of γ-Butyrolactone Signaling Molecules in Actinomycetes: Discovery of Optical Isomer and Identification of 6-Hydroxy-γ-Butyrolactones

○Yuta Kudo1,2, Keiichi Konoki2, Mari Yotsu-Yamashita2

2025/03/07
Identification of biosynthetic genes of domoic acid from the diatom, Nitzschia navis-varingica, collected in Papua New Guinea

Yasuhiro Ashida1, ○Masaki Mochizuki1, Puilingi Clyde2, Yukari Maeno3, Yuta Kudo4,1, Yuko Cho1, Keiichi Konoki1, Yuichi Kotaki1, Mari Yotsu-Yamashita1

2025/03/05
Synthetic study of a putative biosynthetic intermediate of the paralytic shellfish toxin, saxitoxin

Ryosuke Hirozumi, Yuko Cho, Yuta Kudo, Keiichi Konoki, Kazuo Nagasawa, Mari Yotsu-Yamashita

International Symposium in Okinawa, 2023, on Ciguatera and Related Marine Biotoxins　2023/11/13
Dynamic analysis of saxitoxin biosynthesis and catabolism in the dinoflagellate, Alexandrium catenella affected by nigericin

Yuko Cho, Shigeki Tsuchiya, Takuo Omura, Keiichi Konoki, Yasukatsu Oshima, Mari Yotsu-Yamashita

International Symposium in Okinawa, 2023, on Ciguatera and Related Marine Biotoxins　2023/11/13
Synthesis and identification of decarbamoyloxysaxitoxins in the toxic microalgae for elucidation of saxitoxin biosynthesis

Mari Yotsu-Yamashita, Mayu Hakamada, Chihiro Tokairin, Hayate Ishizuka, Kanna Adachi, Toma Osawa, Ryosuke Hirozumi, Yuko Cho, Yuta Kudo, Keiichi Konoki, Yasukatsu Oshima, Kazuo Nagasawa

nternational Symposium in Okinawa, 2023, on Ciguatera and Related Marine Biotoxins　2023/11/13
Colchicine induced dynamic changes in saxitoxin biosynthesis and metabolism in the dinoflagellate Alexandrium pacificum (Group IV)

Yuko Cho, Shigeki Tsuchiya, Takuo Omura, Kazuhiko Koike, Keiichi Konoki, Yasukatsu Oshima, Mari Yotsu-Yamashita

20th International Conference on Harmful Algae　2023/11/09
MS-guided discovery of novel tricyclic guanidino compounds from tetrotodoxin-bearing newts and new analogues of antimalarial phosphotriester salinipostin from actinobacteria

Yuta Kudo, Charles T. Hanifin, Keiichi Konoki, Mari Yotsu-Yamashita

2023/10/16
12β-デオキシ-デカルバモイロキシサキシトキシンの有毒藍藻からの同定

山下まり, 袴田真有, 石塚颯, 安達栞菜, 大澤瞳生, 長由扶子, 工藤雄大, 此木敬一, 大島泰克, 長澤和夫

令和５年度日本水産学会秋季大会　2023/09/21
ColchicineがSTX生産渦鞭毛藻のアミノ酸生合成に及ぼす影響

長由扶子, 小池一彦, 此木敬一, 大島泰克, 山下まり

令和５年度日本水産学会秋季大会　2023/09/21
Structures of new tricyclic guanidino compounds from toxic newt and phosphotriesters from bacteria

Yuta Kudo, Charles T. Hanifin, Keiichi Konoki, Mari Yotsu-Yamashita

International Symposium for the 80th Anniversary of the Tohoku Branch of the Chemical Society of Japan (2023 Joint Meeting of the Tohoku Area Chemistry Societies)　2023/09/10
Evaluation of inhibitory activities of synthetic saxitoxin derivatives to voltage-gated sodium channels

Takumi Kobayashi, Shutaro Yoshio, Osamu Chiba, Ayato Nureki, Yuka Takayanagi, Hayate Ishizuka, Yuta Kudo, Yuko Cho, Mari Yotsu-Yamashita, Kazuo Nagasawa, Keiichi Konoki

Tohoku University GP-Chem Chemistry Summer School 2023　2023/08/09
Synthesis and identification of decarbamoyloxysaxitoxins in the toxic microalgae for elucidation of saxitoxin biosynthesis

Mayu Hakamada, Chihiro Tokairin, Hayate Ishizuka, Kanna Adachi, Toma Osawa, Ryosuke Hirozumi, Yuko Cho, Yuta Kudo, Keiichi Konoki, Yasukatsu Oshima, Kazuo Nagasawa, Mari Yotsu-Yamashita

Tohoku University GP-Chem Chemistry Summer School 2023　2023/08/09
Synthetic study of a putative biosynthetic intermediate of the paralytic shellfish toxin, saxitoxin

Ryosuke Hirozumi, Yuko Cho, Yuta Kudo, Keiichi Konoki, Kazuo Nagasawa, Mari Yotsu-Yamashita

Tohoku University GP-Chem Chemistry Summer School 2023　2023/08/09
H⁺/K⁺ Ionophore, nigericin reduces saxitoxin biosynthesis and enhances its metabolism in the dinoflagellate, Alexandrium catenella (Group I)

Yuko Cho, Shigeki Tsuchiya, Takuo Omura, Keiichi Konoki, Yasukatsu Oshima, Mari Yotsu-Yamashita

Gordon Research Conference, Mycotoxins and Phycotoxins
アミノ酸輸送体阻害剤が渦鞭毛藻 STX 生合成に及ぼす影響の動的解析

長由扶子, 土屋成輝, 大村卓朗(LAS, 此木敬一, 大島泰克, 山下まり

令和５年度日本水産学会春季大会　2023/03/28
致死性海藻中毒原因物質ポリカバノシド類の作用機序

山下まり, 土肥裕花, 北大院農, 岩崎浩太郎, 佐々木理, 川島悠岐, 大院生命, 島田紀子, 大院農, 工藤雄大, 東北大学際研, 東北大院農, 長由扶子, 此木敬一, 佐々木誠

令和５年度日本水産学会春季大会　2023/03/28
サキシトキシンC11位第三級アルコール型誘導体の合成と電位依存性Naチャネル阻害活性評価

前野華子, 濡木絢斗, 高栁優夏, 石塚颯, 千葉修, 吉尾柊太郎, 小林巧, 広川貴次, 此木敬一, 山下まり, 長澤和, 東農工大院工, 東北大院農, 筑波大医学

日本化学会第103春季年会　2023/03/24
海産毒マイトトキシンの脂質膜に対する影響

今田皇緑, 木下祥尚, 此木敬一, 松森信

日本化学会第103春季年会　2023/03/24
Synthetic study of a putative biosynthetic intermediate of paralytic shellfish toxin, saxitoxin

○Ryosuke Hirozumi, Yuko Cho, Yuta Kudo, Keiichi Konoki, Kazuo Nagasawa, Mari Yotsu-Yamashita, Tohoku Univ. Agri, Tohoku Univ. FRIS, Tokyo Univ. of Agri, Te

The 2023 Annual Meeting of The Japan Society for Bioscience, Biotechnology and Agrochemistry　2023/03/15
Mode of action of inhibitory activities of polyunsaturated fatty acids against voltage-gated sodium channels

○Shutaro YOSHIO, Osamu CHIBA, Noriko SHIMADA, Yuta KUDO, Yuko CHO, Mari YOTSU-YAMASHITA, Keiichi KONOKI, Tohoku, Univ. Agri, Tohoku Univ. FRIS

The 2023 Annual Meeting of The Japan Society for Bioscience, Biotechnology and Agrochemistry　2023/03/15
Evaluation of inhibitory activities of synthetic saxitoxin derivatives to voltage-gated sodium channels

Takumi Kobayashi, Shutaro Yoshio, Osamu Chiba, Ayato Nureki, Yuka Takayanagi, Hayate Ishizuka, Yuta Kudo, Yuko Cho, Mari Yotsu-Yamashita, Kazuo Nagasawa, Keiichi Konoki, Tohoku, Univ. Agri, Tokyo Univ. of, Agri. & Tech, Tohoku Univ. FRIS

The 2023 Annual Meeting of The Japan Society for Bioscience, Biotechnology and Agrochemistry　2023/03/15
Dynamic analysis of the action of colchicine on dinoflagellate saxitoxin biosynthesis by in vivo labeling

○Yuko CHO, Shigeki Tsuchiya, Takuo Omura, Kazuhiko Koike, Keiichi Konoki, Yasukatsu Oshima, Mari Yotsu-Yamashita, Tohoku Univ. Agr, LASC, Hiroshima Univ, Integ, Sci. Life, Tohoku Univ. Life Sci

The 2023 Annual Meeting of The Japan Society for Bioscience, Biotechnology and Agrochemistry　2023/03/14
Synthesis of predicted biosynthetic intermediates of saxitoxin, and their identification in a toxic cyanobacterium and dinoflagellates

○Mayu Hakamada, Hayate Ishizuka, Kanna Adachi, Toma Osawa, Chihiro Tokairin, Yuko Cho, Yuta Kudo, Keiichi Konoki, Yasukatsu Oshima, Kazuo Nagasawa, Mari Yotsu-Yamashita, Tohoku Univ. Agri, Tokyo Univ. of, Agri. & Tech, Tohoku Univ. FRIS, Tohoku Univ. Life Sci

The 2023 Annual Meeting of The Japan Society for Bioscience, Biotechnology and Agrochemistry　2023/03/14
Analysis of biosynthetic intermediates of domoic acid in the diatom Nitzschia navis-varingica from Papua New Guinea

○Yasuhiro Ashida, Clyde Puilingi, Motomi Yamada, Yukari Maeno, Yuta Kudo, Yuko Cho, Keiichi Konoki, Yuichi Kotaki, Mari Yotsu-Yamashita, Tohoku Univ. Agri, Pacific Adventist Univ, Tohoku Univ, Grad. Agri, Univ. Tokyo, Grad. Agri, Tohoku Univ. FRIS, Fukushima College

2023/03/14
MS-guided screening, structural elucidation and evaluation of biological activities of new phophotriesters and γ-butyrolactones

○Yuta KUDO, Keiichi KONOKI, Mari YOTSU-YAMASHITA, Tohoku, Univ. FRIS, Tohoku Univ. Agri

The 2023 Annual Meeting of The Japan Society for Bioscience, Biotechnology and Agrochemistry　2023/03/14
Isolation and structural elucidation of a new tetrodotoxin analogue from the pufferfish Chelonodon patoca

○Shiori AONUMA, Yuta KUDO, Yuko CHO, Keiichi KONOKI, Mari YOTSU-YAMASHITA, Tohoku Univ. Agri, Tohoku Univ, Grad. Agri, Tohoku Univ. FRIS

The 2023 Annual Meeting of The Japan Society for Bioscience, Biotechnology and Agrochemistry　2023/03/14
電位依存性ナトリウムチャネルを阻害する核酸アプタマーの探索

小林巧, 鳥海優人, 工藤雄大, 長由扶子, 山下まり, 此木敬一, 東北大院, 農, 東北大, 学際研

令和4年度日本農芸化学会北海道・東北支部合同支部会　2022/09/21
麻痺性貝毒サキシトキシンの二環性推定生合成中間体の合成研究

廣住燎亮,長由扶子,工藤雄大,此木敬一,長澤和夫,山下まり(東北大院・農,東北大・学際研,東農工大院・工)

令和4年度日本農芸化学会北海道・東北支部合同支部会　2022/09/21
放線菌シグナル分子の探索

工藤雄大, 此木敬一, 山下まり(東北大, 学際研, 東北大院

令和4年度日本農芸化学会北海道・東北支部合同支部会　2022/09/21
安定同位体を利用した渦鞭毛藻における窒素同化と STX 生合成の動的解析

長由扶子, 土屋成輝, 大村卓朗, 此木敬一, 大島泰克, 山下まり, 東北大院, 農, LASC, 東北大院

令和4年度日本農芸化学会北海道・東北支部合同支部会　2022/09/21
Preparation of domoic acid and kainic acid analogues using the cyclases, and evaluation of their toxicities

Motomi Yamada, Yukari Maeno, Yuichi Kotaki, Ryuta Terada, Masafumi Hidaka, Yuta Kudo, Yuko Cho, Keiichi Konoki, Mari Yotsu-Yamashita, Graduate School of Agricultural Science, Tohoku University, Fukushima College, United Graduate, School of Agricultural Science, Kagoshima University, Frontier Research Institute for Interdisciplinary Science, Tohoku Universi

The 64th Symposium on the Chemistry of Natural Productse 4　2022/09/08
Synthetic Studies of the Macrocyclic Lactam Structure in Zetekitoxin AB

Hayate Ishizuka, Keiichi Konoki, Mari Yotsu-Yamashita, Kazuo Nagasawa

The 64th Symposium on the Chemistry of Natural Products　2022/09/08
渦鞭毛藻における麻痺性貝毒の生合成 Invited

長由扶子, 日出間志寿, 大村卓朗, 土屋成輝, 小池一彦, 小池香苗, 及川寛, 此木敬一, 大島泰克, 山下まり

令和4年度日本水産学会春季大会ミニシンポジウム　2022/03/29
フグ毒テトロドトキシンの生合成経路の推定 Invited

山下まり, 工藤雄大, 上山望, Charles T. Hanifin, 沼野聡, 長由扶子, 此木敬一

令和4年度日本水産学会春季大会ミニシンポジウム　2022/03/29
12β-deoxysaxitoxin の藍藻 Dolichospermum circinale (TA04)および渦鞭毛藻 Alexandrium pacificum (Group IV)からの同定

山下まり, 赤松みちる, 長由扶子, 此木敬一, 工藤雄大, 大島泰克

令和4年度日本水産学会春季大会　2022/03/28
渦鞭毛藻細胞における麻痺性貝毒成分の蛍光標識アプタマーによる可視化法の検討

長由扶子, 大村卓朗, 小池一彦, 此木敬一, 大島泰克, 山下まり

令和4年度日本水産学会春季大会　2022/03/28
Development of an introduction of a tertiary hydroxyl group at C11 in the saxitoxin (STX) skeleton and application to the synthesis of a new STX derivative

The 102nd CSJ Annual Meeting (2022)　2022/03/23
Evaluation of cross-reactivity of the anti-tetrodotoxin monoclonal antibody against major tetrodotoxin analogues in pufferfish

Keita YAMAKI, Kyoka SATO, Yuta KUDO, Kentaro KAWATSU, Osamu ARAKAWA, Tomohiro TAKATANI, Yuko CHO, Keiichi KONOKI, Mari YAMASHITA

The 2022 Annual Meeting of Japan Society for Bioscience, Biotechnology, and Agrochemistry　2022/03/17
Preparation of a novel kainic acid analogue using the heterologously expressed cyclization enzyme

Motomi YAMADA, Yukari MAENO, Yuichi KOTAKI, Ryuta TERADA, Yuta KUDO, Yuko CHO, Keiichi KONOKI, Mari YOTSU-YAMASHITA

The 2022 Annual Meeting of Japan Society for Bioscience, Biotechnology, and Agrochemistry　2022/03/16
Expression, subcellular localization and activity of saxitoxin biosynthetic enzyme, SxtG in dinoflagellates

Yuko CHO, Shizu Hidema, Takuo Omura, Shigeki Tsuchiya, Kazuhiko Koike, Keiichi Konoki, Yasukatsu Oshima, Mari Yamashit

The 2022 Annual Meeting of Japan Society for Bioscience, Biotechnology, and Agrochemistry　2022/03/16
Synthesis of a predicted biosynthetic intermediate of saxitoxin, and its identification in a toxic freshwater cyanobacterium

Mayu Hakamada, Chihiro Tokairin, Yuko Cho, Kanna Adachi, Hayate Ishizuka, Yuta Kudo, Keiichi Konoki, Yasukatsu Oshima, Kazuo Nagasawa, Mari Yamashit

The 2022 Annual Meeting of Japan Society for Bioscience, Biotechnology, and Agrochemistry　2022/03/16
Two novel skeletal tricyclic guanidino compounds from the tetrodotoxin-bearing newt

Yuta Kudo, Charles T. Hanifin, Yuko Cho, Keiichi Konoki, Mari Yotsu-Yamashita

The 2022 Annual Meeting of Japan Society for Bioscience, Biotechnology, and Agrochemistry　2022/03/16
二次元 NMR long range-HSQMBC を用いた構造解析の有用性の検証

工藤雄大, 海原大輔, Charles T. Hanifi, 長由扶子, 此木敬一, 山下まり, 東北大学際研, 東北大院農, 東北大多元研, タ州立大生

日本農芸化学会東北支部第156 回大会　2021/10/09
生合成酵素を用いたドウモイ酸類縁体の調製と構造活性相関

前野優香理, 小瀧裕一, 寺田竜太, 日高將文, 長由扶子, 此木敬一, 山下まり, 東北大院農, 福島学院大, 鹿児島大院

日本農芸化学会東北支部第156 回大会　2021/10/09
Synthesis, Structure Confirmation, and Biological Activity of the WXYZA'B'C'D'E'F' Ring Segment of Maitotoxin

Keitaro Umeno, Hisaaki Onoue, Yuta Watanabe, Keiichi Konoki, Masayuki Satake, Kohei Torikai, Yoko Yasuno, Tohru Oishi

The 63nd Symposium on The Chemistry of Natural Products　2021/09/15
Structural Elucidation of Novel Skeletal Tricyclic Guanidino Compounds from the Tetrodotoxin-Bearing Newt, Taricha granulosa

Yuta Kudo, Charles T. Hanifin, Yuko Cho, Keiichi Konoki, Mari Yotsu, Yamashita (Graduate School of Agricultural Science, Tohoku University, Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Department of Biology, Utah State, Un

The 63rd Symposium on the Chemistry of Natural Products　2021/09/17
Screening of the target molecule for maitotoxin Invited

Keiichi Konoki, Ken Matsumoto, Masanao Kinoshita, Shunsuke Tsunogae, Moeka Goto, Shutaro Yoshio, Hiroki Tabata, Yuko Cho, Yoko Yashiroda, Katherine Chan, Amy Hin, Yan Tong, Kamaldeep, Kaur Aulakh, Andrea Habsid, Mari Yotsu-Yamashita, Nobuaki Matsumori, Jason Moffat, Charles Boone, Minoru Yoshida, Michio Murata

The 8th symposium of Frontier Research in Chemical Communications, a Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed area)　2021/07/02
テトロドトキシン類縁体のマウス毒性の再確認およびテトロドトキシンのアルカリ初期分解物の単離と構造

山下まり, 八重樫優士, 佐藤恭佳, 杉本亜津子, 長由扶子, 此木敬一

令和三年度日本水産学会春季大会　2021/03/27
渦鞭毛藻サキシトキシン生合成への輸送体阻害剤の影響

長由扶子, 土屋成輝, 日出間志寿, 大村卓朗(LAS, 此木敬一, 大島泰克, 山下まり

令和三年度日本水産学会春季大会　2021/03/27
マイトトキシンのW-F'環部の合成研究

梅野圭太郎, 尾上久晃, 此木敬一, 鳥飼浩平, 保野陽子, 大石徹

日本化学会第101春季年会（2021）　2021/03/20
Synthesis of new saxitoxin derivatives bearing substituents at C11 and evaluation their voltage-gated sodium channel inhibitory activity

2021/03/19
Synthesis of a predicted biosynthetic intermediate of paralytic shellfish toxin, saxitoxin, and its identification in the toxic dinoflagellates

○Chihiro Tokairin, Yuko Cho, Kanna Adachi, Hayate Ishizuka, Keiichi Konoki, Hiroshi Oikawa, Kazuhiko Koike, Kazuo Nagasawa, Mari Yotsu-Yamashita

The 2021 Annual Meeting of JSBBA　2021/03/20
Intracellular localization of SxtA and a hypothesis for the loss of saxitoxin biosynthesis in a dinoflagellate

○Yuko CHO, Shizu Hidema, Takuo Omura, Kazuhiko Koike, Kanae Koike, Hiroshi Oikawa, Keiichi Konoki, Yasukatsu Oshima, Mari Yotsu-Yamashita

The 2021 Annual Meeting of JSBBA　2021/03/20
Mode of action and evaluation of structure-activity relationship of polycavernosides, the causative toxins of lethal seaweed poisoning

○Yuka Doi, Koraro Iwasaki, Satori Sasaki, Yuki Kawashima, Noriko Shimada, Yuko Cho, Keiichi Konoki, Makoto Sasaki, Mari Yamashit

The 2021 Annual Meeting of JSBBA　2021/03/21
Sensitivity of the voltage-gated sodium channels against synthetic saxitoxin derivatives

○Osamu CHIBA, Tomoshi YAMADA, Shunsuke TSUNOGAE, Noriko SHIMADA, Yuko CHO, Yuka TAKAYANAGI, Minami HOSHI, Kanna ADACHI, Hayate ISHIZUKA, Kazuo NAGASAWA, Mari YOTSU-YAMASHITA, Keiichi KONOKI

The 2021 Annual Meeting of JSBBA　2021/03/20
Screening of voltage-gated sodium channel blockers from the marine sponge Halichondria okadai

○Noriko Shimada, Osamu Chiba, Shunsuke Tsunogae, Yuko Cho, Mari Yotsu-Yamashita, Keiichi Konoki

The 2021 Annual Meeting of JSBBA　2021/03/20
Screening for metabolites of paralytic shellfish toxins in the scallop, Patinopecten yessoensis

Satoshi Numano, Yuta Kudo, Yuko Cho, Keiichi Konoki, Mari Yotsu-Yamashita

The 2021 Annual Meeting of JSBBA　2021/03/19
A model reaction for preparation of tetrodotoxin-protein conjugates, and elucidation of the structure of the major product

○Mizuho Zen, Yuta Kudo, Yuko Cho, Keiichi Konoki, Mari Yotsu-Yamashita

The 2021 Annual Meeting of JSBBA　2021/03/19
The novel tetrodotoxin related compounds from pufferfish

○Yuji Yaegashi, Nozomi Ueyama, Yuta Kudo, Yuko Cho, Keiichi Konoki, Mari Yotsu-Yamashita

The 2021 Annual Meeting of JSBBA　2021/03/19
Production of domoic acid analogs using biosynthetic enzyme

○Yukari MAENO, Yuichi KOTAKI, Ryuta TERADA, Yuko CHO, Keiichi KONOKI, Mari YOTSU-YAMASHITA

The 2021 Annual Meeting of JSBBA　2021/03/19
ホタテガイ中腸腺由来オカダ酸アシル基転移酵素の可溶化条件の検討

〇駒崎有紀1、寺内将斗1、工藤雄大1,2、長由扶子1、山下まり1、此木敬一1

2020年度東北支部シンポジウム　2020/11/08
生合成環化酵素を用いたドウモイ酸新規類縁体生産系の構築

前野優香理, 小瀧裕一, 寺田竜太, 長由扶子, 此木敬一, 山下まり

2020年度東北支部シンポジウム　2020/11/08
海洋生物毒スピロリドのスピロイミン環部分構造の合成および4位立体配置の解明

南野宏, 林翔, 村田道雄, 島田紀子, 此木敬一, 土川博史

第62回天然有機化合物討論会　2020/09/22
コルヒチン存在下の渦鞭毛藻サキシトキシン生合成のメタボロミクス解析

長由扶子, 土屋成輝, 小池一彦, 此木敬一, 大島泰克, 山下まり

令和 2 年度日本水産学会春季大会　2020/03/29
高純度テトロドトキシン類縁体の定量と Nav 阻害活性

山下まり, 佐藤恭佳, 千葉修, 長由扶子, 此木敬一

令和 2 年度日本水産学会春季大会　2020/03/29
Screening of inhibitors against voltage-gated sodium channels from the marine sponge Halichondria okadai

2020/03/28
Screening for target molecule of maitotoxin, the most toxic marine natural product

Shunsuke Tsunogae, Katherine Chan, Amy Hin Yan Tong, Kamaldeep Kaur Aulakh, Andrea Habsid, Ken Matsumoto, Yoko Yashiroda, Jason Moffat, Charles Boone, Mari Yotsu-Yamashita, Michio Murata, Minoru Yoshida, Keiichi Konoki

2020/03/28
Synthesis of predicted biosynthetic intermediates of paralytic shellfish toxin, saxitoxin, and analysis of these compounds in toxin producing microorganisms

2020/03/26
Isolation and structure elucidation of novel tetrodotoxin related compounds from pufferfish

2020/03/26
Synthesis of saxitoxin enantiomers and evaluation of their inhibitory activity towards sodium channel

○TAKAYANAGI, Yuka, ADACHI, Kanna, ISHIZUKA, Hayate, CHIBA, Osamu, KONOKI, Keiichi, YOTSU-YAMASHITA, Mari, ODAGI, Minami, NAGASAWA, Kazuo

2020/03/24
Efficient Synthesis of 7,6-Spirocyclic Imine and Stereochemical Determination of Marine Toxin Spirolide Homologues

○MINAMINO, Kou, TSUCHIKAWA, Hiroshi, MURATA, Michio, SHIMADA, Noriko, KONOKI, Keiichi
致死性海藻中毒原因物質ポリカバノシド類の作用機序

山下まり, 土肥裕花, 島田紀子, 岩崎浩太郎, 佐々木理, 川島悠岐, 此木敬一, 佐々木誠

新学術領域研究「化学コミュニケーションのフロンテイア」第6回公開シンポジウム　2019/12/09
Elucidation of mode of action for marine natural toxins Invited

Keiichi Konoki

2019/12/03
ドウモイ酸とカイニン酸の新規関連化合物の単離，構造決定と生合成経路

前野優香理, 小瀧裕一, 寺田竜太, 長由扶子, 此木敬一, 山下まり

第61回天然有機化合物討論会　2019/11/12
Crisprスクリーニングによる maitotoxin の標的分子探索（２）

角替俊輔, Katherine Chan, Amy Hin Yan Tong, Kamaldeep Kaur Aulakh, Andrea Habsid, 八代田陽子, Jason Moffat, Charles Boone, 山下まり, 村田道雄, 此木敬一

公益社団法人日本農芸化学会東北支部・第154回大会　2019/11/09
Crisprスクリーニングによる maitotoxin の標的分子探索（１）

角替俊輔, Katherine Chan, Amy Hin Yan Tong, Kamaldeep Kaur Aulakh, Andrea Habsid, 八代田陽子, Jason Moffat, Charles Boone, 山下まり, 村田道雄, 此木敬一

公益社団法人日本農芸化学会東北支部・第154回大会　2019/11/09
淡水産藍藻 Anabaena circinalis (TA04 株)における新規麻痺性貝毒類縁体の探索

赤松みちる, 長由扶子, 此木敬一, 山下まり

公益社団法人日本農芸化学会東北支部・第154回大会　2019/11/09
C11位炭素置換型サキシトキシン誘導体の合成と活性評価

安達栞菜, 石塚颯, 山田智士, 日高將文, 広川貴次, 小田木陽, 此木敬一, 山下まり, 長澤和夫

第61回天然有機化合物討論会　2019/09/11
Isolation and structural elucidation of tetrodotoxin related compounds from pufferfish

Yaegashi, Y., Ueyama, N., Kudo, Y., Cho, Y., Konoki, K., Yotsu-Yamashita, M.
Screening of novel secondary metabolites from microorganisms associated with the marine sponge Halichondria okadai,

Goto, M., Kikuchi, S., Okada, K., Cho, Y., Yotsu-Yamashita, M., Konoki, K.

Tohoku University’s Chemistry Summer School
Identification of biosynthetic intermediates of amnesic shellfish toxin domoic acid and anthelmintic compound kainic acid

Gordon Research Conference, Mycotoxins and Phycotoxins　2019/06/17
Metabolomic study of saxitoxin biosynthesis in dinoflagellates using 15N-labelled sodium nitrate as a nitrogen source

Gordon Research Conference, Mycotoxins and Phycotoxins
渦鞭毛藻の麻痺性貝毒生合成に対する 5-ethynyl-2’-deoxyuridine の影響と作用点

長由扶子, 土屋成輝, 大村卓朗, 小池一彦, 此木敬一, 大島泰克, 山下まり

平成31年度公益社団法人日本水産学会春季大会　2019/03/28
高純度テトロドトキシン類縁体の調製

山下まり, 佐藤恭佳, 工藤雄大, 長由扶子, 此木敬一

平成31年度公益社団法人日本水産学会春季大会　2019/03/28
テトロドトキシン推定生合成中間体のテトロドトキシン含有生物への投与

杉本敬太, 工藤雄大, 宮坂忠親, 安立昌篤, 長由扶子, 此木敬一, 千葉親文, 西川俊夫, 山下まり

日本農芸化学会2019年度大会　2019/03/26
渦鞭毛藻におけるサキシトキシン生合成の15N同位体標識硝酸ナトリウムを用いたメタボロミクス解析

長由扶子, 土屋成輝, 大村卓朗, 小池一彦, 及川寛, 此木敬一, 大島泰克, 山下まり

日本農芸化学会2019年度大会　2019/03/26
東日本で養殖したホタテガイ中のLC-MS/MSによる麻痺性貝毒分析

沼野聡, 工藤雄大, 長由扶子, 此木敬一, 山下まり

日本農芸化学会2019年度大会　2019/03/26
カイニン酸新規類縁体の探索及び生合成経路の推定

前野優香理, 寺田竜太, 小瀧裕一, 長由扶子, 此木敬一, 山下まり

日本農芸化学会2019年度大会　2019/03/26
ソロモン諸島産の海洋生物中のNav阻害活性物質の探索

春日政人, Clyde Gorapava Puilingi, 角替俊輔, 中崎敦夫, 長由扶子, 西川俊夫, 此木敬一, 山下まり

日本農芸化学会2019年度大会　2019/03/24
電位依存性ナトリウムチャネルに対するサキシトキシン誘導体の阻害活性評価

山田智士, 安達栞菜, 長由扶子, 山下まり, 此木敬一, 長澤和夫

日本農芸化学会2019年度大会　2019/03/24
ホタテガイ中腸腺のオカダ酸アシル化酵素の探索に向けた活性測定法の開発

寺内将斗, 古用幸愛, 長由扶子, 山下まり, 此木敬一

日本農芸化学会2019年度大会　2019/03/24
スピロイミン環を有する海洋天然物の生物活性中心構造の合成とそのニコチン性アセチルコリン受容体阻害能の評価

南野宏, 土川博史, 村田道雄, 此木敬一

日本化学会第99春季年会2019　2019/03/16
C11位に着目した新規サキシトキシン誘導体の合成及びパッチクランプ法を用いたNaチャネル阻害活性評価

星美波, 安達栞菜, 山田智士, 大木麻菜, 石塚颯, 此木敬一, 山下まり, 長澤和夫

日本化学会第99春季年会2019　2019/03/16
Sensitivity of the voltage-gated sodium channel subtypes, Nav1.1 to Nav1.7, against guanidine-containing natural products and their analogues International-presentation

Tadaaki Tsukamoto, Yukie Chiba, Shunsuke Tsunogae, Tomoshi Yamada, Yuko Cho, Ryo Sakakibara, Takuya Imazu, Shouta Tokoro, Yoshiki Satake, Yuki Ishikawa, Yoshiki Nakane, Masaatsu Adachi, Atsuo Nakazaki, Toshio Nishikawa, Minoru Wakamori, Mari Yotsu-Yamashita, Keiichi Konoki

2019/01/09
テトロドトキシン類縁体に対する電位依存性ナトリウムチャネルの感受性評価

塚本匡顕, 千葉雪絵, 若森実, 日高將文, 山田智士, 角替俊輔, 長由扶子, 榊原良, 今津拓也, 所聖太, 佐竹佳樹, 安立昌篤, 西川俊夫, 山下まり, 此木敬一

第60回天然有機化合物討論会　2018/09/26
マイトトキシンの膜透過性亢進作用の機構解明に向けた電気生理学的アプローチ

山田智士, 岩本真幸, 長由扶子, 老木成稔, 村田道雄, 山下まり, 此木敬一

日本農芸化学会東北・北海道合同支部大会（東北支部第153回大会）　2018/09/22
ホタテガイ中腸腺に存在するオカダ酸アシル化酵素の探索法の開発

寺内将斗, 古用幸愛, 長由扶子, 山下まり, 此木敬一

日本農芸化学会東北・北海道合同支部大会（東北支部第153回大会）　2018/09/22
Screening for bioactive compounds in marine organisms collected in the Solomon Islands International-presentation

Masato Kasuga, Clyde Gorapava Puilingi, Atsuo Nakazaki, Shunsuke Tsunogae, Yuko Cho, Keiichi Konoki, Toshio Nishikawa, Mari Yotsu-Yamashita

Tohoku University's Chemistry Summer School　2018/08/27
Bioconversion of putative biosynthetic intermediates of amnesic shellfish toxin, domoic acid, in the diatom Pseudo-nitzschia multiseries International-presentation

Yukari Maeno, Yuichi Kotaki, Yuko Cho, Keiichi Konoki, Mari Yotsu-Yamashita

Tohoku University's Chemistry Summer School　2018/08/27
記憶喪失性貝毒ドウモイ酸の新規生合成中間体の同定と生合成経路の解明

前野優香理, 小瀧裕一, 寺田竜太, 長由扶子, 此木敬一, 山下まり

2018/06/09
紅藻ハナヤナギ(Chondria armata)から同定したドウモイ酸の推定生合成中間体のLC-MS分析法の検討

前野優香理, 山下まり, 長由扶子, 此木敬一, 小瀧裕一, 寺田竜太

平成30年度日本水産学会春季大会　2018/03/26
15N同位体標識培地による渦鞭毛藻の麻痺性貝毒及び生合成中間体への15N取り込み挙動の解析

長由扶子, 土屋成輝, 此木敬一, 大島泰克, 山下まり

平成30年度日本水産学会春季大会　2018/03/26
Synthesis and biological evaluation of natural product- mimicking 7,6-spirocyclic imine compounds toward a specific inhibitor of neuronal nicotinic acetylcholine receptor

○Kou Minamino, Hiroshi Tsuchikawa, Michio Murata, Keiichi Konoki

日本化学会第98春季年会 (2018)　2018/03/20
記憶喪失性貝毒ドウモイ酸の生合成経路に関する研究

前野優香理, 小瀧裕一, 長由扶子, 此木敬一, 山下まり

日本農芸化学会2018年度大会　2018/03/15
クロイソカイメン共生菌が生産する新規有毒二次代謝産物の構造決定

菊池颯, 岡田華弥, 長由扶子, 吉田慎一朗, 權垠相, 山下まり, 此木敬一

日本農芸化学会2018年度大会　2018/03/15
海洋生物における新規テトロドトキシン関連化合物の探索

上山望, 杉本敬太, 長由扶子, 此木敬一, 山下まり

日本農芸化学会2018年度大会　2018/03/15
フグ由来のテトロドトキシン関連化合物の合成

杉本敬太, 上山望, 長由扶子, 此木敬一, 西川俊夫, 山下まり

日本農芸化学会東北支部第152回大会　2017/11/04
フグの新規スピロ環状グアニジノ化合物の単離,構造決定と海産テトロドトキシンの生合成経路の推定

上山望, 杉本敬太, 工藤雄大, 長由扶子, 此木敬一, 西川俊夫, 山下まり

第59回天然有機化合物討論会　2017/09/20

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90秒の口頭発表を含む
化学合成に基づいたマイトトキシンの構造活性相関研究

尾上久晃, 石川絵理奈, 丸林里帆, 此木敬一, 鳥飼浩平, 海老根真琴, 大石徹

第59回天然有機化合物討論会　2017/09/20

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90秒の口頭発表を含む
Screening of novel toxic secondary metabolites from symbiotic bacteria of the marine sponge Halichondria okadai International-presentation

Sou Kikuchi, Kayo Okada, Yuko Cho, Mari Yotsu-Yamashita, Keiichi Konoki

Tohoku University's Chemistry Summer School 2017　2017/08/21
Screening of biosynthetic intermediates of domoic acid, the causative toxin of amnesic shellfish poisoning International-presentation

Yukari Ebine, Yuichi Kotaki, Ryuta Terada, Yuko Cho, Keiichi Konoki, Mari Yotsu-Yamashita

Tohoku University's Chemistry Summer School 2017　2017/08/21
電位依存性Na+チャネルに対するCrambescin B誘導体の阻害活性

塚本匡顕, 千葉雪絵, 中崎敦夫, 石川裕生, 中根嘉祈, 長由扶子, 西川俊夫, 山下まり, 此木敬一

第12回化学生態学研究会　2017/06/23
渦鞭毛藻有毒、無毒種の STX 生合成中間体定量と推定 STX 生合成酵素 SxtA4 の発現解析

°長由扶子, 土屋成輝, 日出間志寿, 大村卓朗(LASC, 小池一彦, 及川寛, 此木敬一, 大島泰克, 山下まり

平成29年度公益社団法人日本水産学会春季大会　2017/03/26
モヨウフグ(Arothron)属3種およびオキナワフグ(Chelonodon patoca)血漿中のテトロドトキシン類と PSTBP 類似タンパク質の解析

長岡佑真, 村本光二, 長由扶子, 此木敬一, 山下まり

平成29年度公益社団法人日本水産学会春季大会　2017/03/26
ベラトリジンによる電位依存性ナトリウムチャネルの不活性化遅延作用に対するクランベシンB類縁体の抑制効果

塚本匡顕, 千葉雪絵, 中崎敦夫, 石川裕生, 中根嘉祈, 長由扶子, 山下まり, 西川俊夫, 此木敬一

日本農芸化学会2017年度大会　2017/03/17

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1東北大院農、2名大院生命農
クロイソカイメン共生菌が生産する新規有毒二次代謝産物の探索

菊池颯, 岡田華弥, 長由扶子, 山下まり, 此木敬一

日本農芸化学会2017年度大会　2017/03/17
渦鞭毛藻の麻痺性貝毒及び生合成中間体のカラムスイッチング HILIC-HILIC-MS-MRMによる分析

長由扶子, 土屋成輝, 吉岡廉平, 大村卓朗, 此木敬一, 大島泰克, 山下まり

日本農芸化学会2017年度大会　2017/03/17

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1東北大農、2LASC、3東北大生命
有毒藍藻 Anabaena circinalis(TA04)からの未知麻痺性貝毒サキシトキシン類縁体の探索

美野輪高之, 長由扶子, 土屋成輝, 此木敬一, 大島泰克, 山下まり

日本農芸化学会2017年度大会　2017/03/17

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1東北大院農、2東北大院生命
フグにおける新規テトロドトキシン関連化合物の探索

上山望, 杉本敬太, 長由扶子, 此木敬一, 山下まり

日本農芸化学会2017年度大会　2017/03/17
記憶喪失性貝毒ドウモイ酸新規関連化合物の探索

海老根優香理, 小瀧裕一, 寺田竜太, 長由扶子, 此木敬一, 山下まり

日本農芸化学会2017年度大会　2017/03/17

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1東北大院農、2北里大海洋、3鹿児島大院連合農
向山アルドール縮合反応を用いた新規サキシトキシン誘導体の合成と活性評価

大木麻菜, 汪超, 原田大資, 塚本匡顕, 此木敬一, 山下まり, 長澤和夫

日本化学会第97春季年会（2017）　2017/03/16
麻痺性貝毒の生合成経路解明に向けた予想生合成中間体の合成及び同定

土屋成輝, 吉岡廉平, 長由扶子, 此木敬一, 長澤和夫, 大島泰克, 山下まり

日本農芸化学会東北支部第151回大会　2016/10/09

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1東北大・院農、2東農工大・院工、3東北大・院生命
トラフグ属(Takifugu)以外の属のフグ血漿中のPSTBP類似タンパク質

長岡佑真, 村本光二, 長由扶子, 此木敬一, 山下まり

日本農芸化学会東北支部第151回大会　2016/10/09

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1東北大・院農、2東北大・院生命
麻痺性貝毒生合成中間体の同定と生合成経路の解明

土屋成輝, 長由扶子, 吉岡廉平, 美野輪高之, 此木敬一, 長澤和夫, 大島泰克, 山下まり

第58回天然有機化合物討論会　2016/09/14

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1東北大院農・2東農工大院工・3東北大院生命
Screening of the biosynthetic intermediates of paralytic shellfish toxins using a stable isotope-labeled precursors International-presentation

Shigeki Tsuchiya, Yuko Cho, Keiichi Konoki, Mari Yotsu-Yamashita

Tohoku University's Chemistry Summer School　2016/08/18
A new sarasinoside from marine sponge Melophlus sarasinorum collected in the Solomon Islands International-presentation

Clyde Gorapava Puilingi, Yuta Kudo, Keiichi Konoki, Yuko Cho, Mari Yotsu-Yamashita

Tohoku University's Chemistry Summer School　2016/08/18
電位依存性ナトリウムチャネルに対するテトロドトキシンおよび類縁体の阻害活性評価

塚本匡顕, 千葉雪絵, 安立昌篤, 榊原良, 所聖太, 今津拓也, 佐竹佳樹, 長由扶子, 西川俊夫, 山下まり, 此木敬一

第9回化学生態学研究会　2016/07/01

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1東北大・院農，2名大・院生命農
新規麻痺性貝毒生合成関連化合物の同定

土屋成輝, 長由扶子, 吉岡廉平, 此木敬一, 長澤和夫, 山下まり

日本農芸化学会2016年度大会　2016/03/27

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1東北大院農、2東京農工大院工
有毒藍藻の細胞破砕液を用いた新規麻痺性貝毒生合成中間体の探索

美野輪高之, 土屋成輝, 長由扶子, 此木敬一, 山下まり

日本農芸化学会2016年度大会　2016/03/27
テトロドトキシンの生合成経路解明を目指した有毒イモリからの推定生合成中間体の探索

工藤雄大, 長由扶子, 此木敬一, 山下まり

日本農芸化学会2016年度大会　2016/03/27
フグから得られた新規テトロドトキシン関連化合物の単離と構造

上山望, 工藤雄大, 長由扶子, 此木敬一, 山下まり

日本農芸化学会2016年度大会　2016/03/27
11-oxoTTXをハプテンとしたポリクローナル抗体の作製とTTX誘導体の生理活性

猿橋祥吾, 長由扶子, 此木敬一, 西川俊夫, 山下まり

日本農芸化学会2016年度大会　2016/03/27

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1東北大院農、2名大院生命農
トラフグ属 (Takifugu) 以外の属のフグ血漿中のPSTBP類似タンパク質の解析

長岡佑真, 長由扶子, 此木敬一, 山下まり

日本農芸化学会2016年度大会　2016/03/27
下痢性貝毒変換酵素のの精製を目指した酵素活性測定法の開発

古用幸愛, 小野田竜也, 長由扶子, 山下まり, 此木敬一

平成２８年度公益社団法人日本水産学会春季大会　2016/03/26
渦鞭毛藻Alexandrium tamarense有毒、無毒株比較研究ー推定STX生合成酵素SxtAの免疫化学的手法によるタンパク質発現解析

長由扶子, 日出間志寿, 土屋成輝, 此木敬一, 大島泰克, 山下まり

平成２８年度公益社団法人日本水産学会春季大会　2016/03/26

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1東北大院農、2東北大院生命
コモンフグ卵巣由来の4,4a-anhydrotetrodotoxinの同定と生理活性

猿橋祥吾, 山下まり, 長由扶子, 此木敬一

平成２８年度公益社団法人日本水産学会春季大会　2016/03/26
電位依存性ナトリウムチャネルに対するテトロドトキシンおよび類縁体の活性阻害評価

塚本匡顕, 千葉雪絵, 長由扶子, 安立昌篤, 榊原良, 所聖太, 今津拓也, 中崎敦夫, 石川裕生, 西川俊夫, 山下まり, 此木敬一

日本農芸化学会東北支部第150回大会　2015/10/03

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1東北大・院農、2名大・院生命農
過去に致死性食中毒を引き起こした原因海藻および海藻付着物中のポリカバノシド類の分析

遠藤嵩英, 前田高輔, 長由扶子, 此木敬一, 山下まり

日本農芸化学会東北支部第150回大会　2015/10/03
イモリにおけるテトロドトキシンの起源および蓄積能の調査と考察

工藤雄大, 千葉親文, 長由扶子, 此木敬一, 山下まり

日本農芸化学会東北支部第150回大会　2015/10/03

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1東北大・院農、2筑波大・生命環境系
有毒イモリから得られた新規環状グアニジン化合物群とテトロドトキシン生合成経路の考察

工藤雄大, 千葉親文, 長由扶子, 此木敬一, 山下まり

第５７回天然有機化合物討論会　2015/09/09

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1東北大院農、2筑波大生命環境系
電位依存性ナトリウムチャネルのサブタイプを識別するテトロドトキシン類縁体の探索

千葉雪絵, 塚本匡顕, 長由扶子, 安立昌篤, 榊原良, 所聖太, 中崎敦夫, 石川裕生, 西川俊夫, 山下まり, 此木敬一

日本農芸化学会2015年度大会　2015/03/26

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1東北大院農、2名古屋大院農
フコキサンチン及びフコキサンチノールに対するポリクローナル抗体の作製と性状

上野美紗, 野村駿, 長由扶子, 此木敬一, 山下まり

日本農芸化学会2015年度大会　2015/03/26
安定同位体標識生合成中間体を用いた麻痺性貝毒生合成研究

土屋成輝, 長由扶子, 此木敬一, 長澤和夫, 大島泰克, 山下まり

日本農芸化学会2015年度大会　2015/03/26

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1東北大院農、2東京農工大院工、3東北大院生命科学
麻痺性貝毒の予想生合成中間体E'の探索と精製

吉岡廉平, 長由扶子, 土屋成輝, 此木敬一, 小柴生造, 大島泰克, 山下まり

日本農芸化学会2015年度大会　2015/03/26

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1東北大院農、2東北大東北メデイカル・メガバンク機構、3東北大院生命科学
有毒イモリからのテトロドトキシンの推定生合成中間体の探索

工藤雄大, 長由扶子, 此木敬一, 山下まり

日本農芸化学会2015年度大会　2015/03/26
ホタテガイ中で進行する下痢性貝毒オカダ酸の構造変換および変換酵素の単離を目指すケミカルバイオロジー

古用幸愛, 小野田竜也, 長由扶子, 山下まり, 此木敬一

日本農芸化学会2015年度大会　2015/03/26
クロイソカイメンに共生する微生物の純化および二次代謝産物の構造研究

岡田華弥, 長由扶子, 山下まり, 此木敬一

日本農芸化学会2015年度大会　2015/03/26
天然毒を貯蔵する生物が獲得した解毒機構

第2回天然物化学研究会　2014/11/21
Analysis of polycavernoside A in the red alga Gracilaria edulis that caused previous fatal food poisonings in Guam and Philippines International-presentation

Mari Yotsu-Yamashita, Kosuke Maeta, Yuki Taya, Eri Omizu, Takahide Endo, Yuko Cho, Keiichi Konoki, Mirriam A. Cayme, Yasuo Fukuyo, Sherwood Hall, Takeshi Yasumoto

The 16th International conference on Harmful Algae　2014/10/27
Identification of 12β-deoxydecarbamoylsaxitoxin in the toxic marine dinoflagellate International-presentation

Yuko Cho, Renpei Yoshioka, Shigeki Tsuchiya, Keiichi Konoki, Yasukatsu Oshima, Mari Yotsu-Yamashita

The 16th International conference on Harmful Algae　2014/10/27
クロイソカイメンおよびホタテガイによる下痢性貝毒の蓄積機構

此木敬一, 古用幸愛, 岡田華弥, 小野田竜也, 小濱真実, 松浦宏樹, 長由扶子, 渡邊龍一, 加賀新之助, 鈴木敏之, 山下まり

第56回天然有機化合物討論会　2014/10/15
クロイソカイメン（Halichondria okadai）共生菌からの有用物質探索

岡田華弥, 長由扶子, 山下まり, 此木敬一

平成26年度日本農芸化学会北海道・東北合同支部大会　2014/09/22
ホタテガイ中のオカダ酸アシル化酵素の探索

古用幸愛, 小野田竜也, 長由扶子, 山下まり, 此木敬一

平成26年度日本農芸化学会北海道・東北合同支部大会　2014/09/22
麻痺性貝毒の生合成経路解明のための藍藻Anabaena circinalis（TA04株）の培養条件等の検討

土屋成輝, 長由扶子, 此木敬一, 山下まり

平成26年度日本農芸化学会北海道・東北合同支部大会　2014/09/22
新規硫酸化フロロタンニンの単離と構造、存在意義の推定

服部純麗, 伊藤久富, 瀬川慎也, 近藤左和子, 長由扶子, 此木敬一, 山下まり

平成26年度日本農芸化学会北海道・東北合同支部大会　2014/09/22
抗テトロドトキシン抗体の開発を目的としたテトロドトキシン-タンパク質複合体調製の検討

猿橋祥吾, 鶴野ひかり, 山口日出起, 金子陸, 長由扶子, 此木敬一, 山下まり

平成26年度日本農芸化学会北海道・東北合同支部大会　2014/09/22
Approach to elucidation of biosynthetic pathways towards tetrodotoxin and saxitoxin International-presentation

Mari Yotsu-Yamashita, Yuta Kudo, Shigeki Tsuchiya, Yuko Cho, Keiichi Konoki

Tohoku University’s Chemistry Summer School　2014/08/25
Screening of tetrodotoxin in pufferfish from Solomon Islands International-presentation

Clyde Gorapava Puilingi, Yuta Kudo, Keiichi Konoki, Yuko Cho, Mari Yotsu-Yamashita

Tohoku Universitiy’s Chemistry Summer School　2014/08/25
Structure elucidation of 10-hemiketal-type tetrodotoxin analogues, indicative of the biosynthetic pathway International-presentation

Yuta Kudo, Yoko Yamashita, Keiichi Konoki, Yuko Cho, Takeshi Yasumoto, Mari Yotsu-Yamashita

Gordon Research Conference, Natural Products　2014/07/20
イチイ由来α、βチューブリンの発現とtaxol結合性の評価

工藤佑馬, 長由扶子, 山下まり, 此木敬一

第9回化学生態学研究会　2014/06/27
オキナワシリケンイモリの新規テトロドトキシン類縁体の構造、および各種有毒イモリにおける分布

工藤雄大, 此木敬一, 長由扶子, 山下まり

第9回化学生態学研究会　2014/06/27
フグ毒テトロドトキシン新規類縁体の構造と生理活性、および含有生物の毒組成解析

工藤雄大, 此木敬一, 長由扶子, 山下まり

第25回記念万有仙台シンポジウム　2014/06/14
渦鞭毛藻Alexandrium tamarense有毒株における微量麻痺性貝毒類縁体の同定

長由扶子, 吉岡廉平, 土屋成輝, 此木敬一, 大島泰克, 山下まり

第28回海洋生物活性談話会　2014/05/10
光親和性標識基を導入したガンビエロール単純化類縁体の合成と生物活性評価

廣田一晃, 菅悠人, 此木敬一, 山下まり, 不破春彦, 佐々木誠

日本化学会第94春季年会　2014/03/27
イチイTaxus cuspidata由来 α、βチューブリンの発現とタキソール結合性の評価

工藤佑馬, 長由扶子, 山下まり, 此木敬一

日本農芸化学会2014年度大会　2014/03/27
10- hemiketal型テトロドトキシン類縁体の構造決定と生合成経路の考察

工藤雄大, 山下瑶子, 此木敬一, 長由扶子, 安元健, 山下まり

日本農芸化学会2014年度大会　2014/03/27
致死性海藻食中毒原因物質ポリカバノシドAの起源生物の推定

前田高輔, 田谷有妃, 大水絵理, Mirriam A. Cayme, 長由扶子, 此木敬一

日本農芸化学会2014年度大会　2014/03/27
ホタテ貝中で進行する下痢性貝毒オカダ酸のアシル化反応

此木敬一, 古用幸愛, 小野田竜也, 長由扶子, 山下まり

日本農芸化学会2014年度大会　2014/03/27
メタゲノムからの新規Baeyer-Villiger monooxygenaseのスクリーニング

山下瑶子, 山下まり, 工藤雄大, 長由扶子, 此木敬一

日本農芸化学会2014年度大会　2014/03/27
麻痺性貝毒の生合成中間体の定量及び未知中間体について

土屋成輝, 長由扶子, 吉岡廉平, 此木敬一, 長澤和夫, 大島泰克, 山下まり

日本農芸化学会2014年度大会　2014/03/27
渦鞭毛藻Alexandrium tamarense有毒株のdcSTX-12α-olの同定

長由扶子, 吉岡廉平, 土屋成輝, 此木敬一, 大島泰克, 山下まり

平成26年度日本水産学会春季大会　2014/03/27
グアムの致死性食中毒発生時に採集されたカタオゴノリのポリカバノシドAの分析

前田高輔, 山下まり, 此木敬一, 長由扶子, Sherwood Hall, 安元健

平成26年度日本水産学会春季大会　2014/03/27
マイトトキシンのQRS環部およびC’D’E’F’環部の合成と生物活性

尾上久晃, 國武政宏, 馬場萌未, 鳥飼浩平, 海老根真琴, 此木敬一, 村田道雄, 大石徹

日本化学会第94春季年会　2014/03/27
ヒト型電位依存性カリウムチャネルKv1.2に対するガンビエロールの相互作用

此木敬一

平成２５年度ERATO村田脂質活性構造プロジェクト研究報告会　2014/03/20
下痢性貝毒に対してクロイソカイメンと二枚貝が獲得した解毒機構

此木敬一

名古屋大学大学院農学生命科学研究科生物有機化学研究室セミナー　2013/12/17
Physiological Function Acquired by Diarrheic Shellfish Poisoning-Accumulating Species International-presentation

Keiichi Konoki

The 2nd International Symposium on Chemical Biology of Natural Products: Target ID and Regulation of Bioactivity　2013/10/28
Synthesis of Marine Toxins Aiming at Developing Ion-Channel Inhibitors International-presentation

Toshio Nishikawa, Masaatsu Adachi, Ryo Sakakibara, Takuya Imazu, Yoshiki Satake, Shouta Tokoro, Atsuo Nakazaki, Yuki Ishikawa, Yusuke Sawayama, Minoru Isobe, Keiichi Konoki, Mari Yotsu-Yamashita

The 2nd International Symposium on Chemical Biology of Natural Products: Target ID and Regulation of Bioactivity　2013/10/28
Nav安定発現系の構築とTTX関連化合物の結合性評価

千葉雪絵, 長由扶子, 安立昌篤, 榊原良, 所聖太, 今津拓也, 磯部稔, 西川俊夫, 山下まり, 此木敬一

日本農芸化学会東北支部会第148回大会　2013/10/26
麻痺製貝毒の生合成中間体の探索

吉岡廉平, 土屋成輝, 長由扶子, 此木敬一, 大島泰克, 山下まり

日本農芸化学会東北支部会第148回大会　2013/10/26
抗フコキサンチンポリクローナル抗体の作製

上野美紗, 野村駿, 此木敬一, 長由扶子, 山下まり

日本農芸化学会東北支部会第148回大会　2013/10/26
クロイソカイメンおよびホタテ貝による下痢性貝毒の蓄積機構

此木敬一

日本農芸化学会東北支部会第148回大会　2013/10/26
5-Fluoro-2’-deoxyuridine influenced the growth and the biosynthesis of intermediates for paralytic shellfish toxins of the dinoflagellate, Alexandrium tamarense International-presentation

Yuko Cho, Shigeki Tsuchiya, Keiichi Konoki, Yasukatsu Oshima, Mari Yotsu-Yamashita

International Symposium for the 70th Anniversary of the Tohoku Branch Chemical Society of Japan　2013/09/28
Synthesis and identification of putative biosynthetic intermediates in early stage for paralytic shellfish toxins International-presentation

Shigeki Tsuchiya, Yuko Cho, Keiichi Konoki, Kazuo Nagasawa, Yasukatsu Oshima, Mari Yotsu-Yamashita

International Symposium for the 70th Anniversary of the Tohoku Branch Chemical Society of Japan　2013/09/28
Identification of 5,11-dideoxytetrodotoxin in marine animals, and characterization of ESI-MS fragment ions of tetrodotoxin and its analogs International-presentation

Mari Yotsu-Yamashita, Yuka Abe, Yuta Kudo, Keiichi Konoki, Yuko Cho, Toshio Nishikawa, Minoru Isobe

International Symposium for the 70th Anniversary of the Tohoku Branch Chemical Society of Japan　2013/09/28
The structure of the novel tetrodotoxin analog, 6-deoxytetrodotoxin, and structure activity relationship study on C-6 and C-11 hydroxyl groups of tetrodotoxin International-presentation

Mari Yotsu-Yamashita, Yuka Abe, Yuta Kudo, Keiichi Konoki, Yuko Cho, Toshio Nishikawa, Minoru Isobe

International Symposium for the 70th Anniversary of the Tohoku Branch Chemical Society of Japan　2013/09/28
In vitro acylation of okadatic acid in the presence of various bivalves' extracts International-presentation

Keiichi Konoki, Tatsuya Onoda, Ryuichi Watanabe, ○Sachie Furumochi, Yuko Cho, Shinnosuke Kaga, Toshiyuki Suzuki, Mari Yotsu-Yamashita

International Symposium for the 70th Anniversary of the Tohoku Branch Chemical Society of Japan　2013/09/28
Interaction of taxol with tubulins form Taxus cuspidata International-presentation

Yuma Kudo, Yuko Cho, Mari Yotsu-Yamashita, Keiichi Konoki

International Symposium for the 70th Anniversary of the Tohoku Branch Chemical Society of Japan　2013/09/28
新規テトロドトキシン類縁体の構造と生合成経路の推定

工藤雄大, 山下瑤子, 此木敬一, 長由扶子, 安元健, 山下まり

第55回天然有機化合物討論会　2013/09/18
Screening of new tetrodotoxin analogues using HILIC-LC-MS/MS and their structure determination International-presentation

Yuta Kudo, Keiichi Konoki, Yuko Cho, Mari Yotsu-Yamashita

Tohoku University Campus Asia Summer School 2013　2013/08/29
Synthesis of putative biosynthetic intermediates in early stage for paralytic shellfish toxins, and their identification in toxin producing microorganisms International-presentation

Shigeki Tsuchiya, Yuko Cho, Keiichi Konoki, Kazuo Nagasawa, Yasukatsu Oshima, Mari Yotsu-Yamashita

Tohoku Universitiy’s Chemistry Summer School　2013/08/28
Screening of new tetrodotoxin analogues using HILIC-LC-MS/MS and their structure determination International-presentation

Yuta Kudo, Keiichi Konoki, Yuko Cho, Mari Yotsu-Yamashita

Tohoku Universitiy’s Chemistry Summer School　2013/08/28
オキナワシリケンイモリの新規テトロドトキシン類縁体の構造、および各種有毒イモリにおける分布

工藤雄大, 此木敬一, 長由扶子, 山下まり

第８回化学生態学研究会　2013/06/28
オカダ酸貯蔵生物が獲得した生理機能

Kayo Okada, Tatsuya Onoda, Yuko Cho, Mari Yotsu-Yamashita, Keiichi Konoki

第８回化学生態学研究会　2013/06/28
下痢性貝毒貯蔵生物における自己耐性機構の探索

小野田竜也, 渡邊龍一, 長由扶子, 加賀新之助, 鈴木敏之, 山下まり

日本農芸化学会2013年度仙台大会　2013/03/24
クロイソカイメン中でオカダ酸およびオカダ酸結合タンパク質OABP2を生産する生物の探索

小濱真実, 岡田華弥, 西谷豪, 長由扶子, 山下まり

日本農芸化学会2013年度仙台大会　2013/03/24
麻痺性貝毒生合成初期中間体の合成と毒生産生物からの同定

土屋成輝, 長由扶子, 長澤和夫, 大島泰克, 山下まり

日本農芸化学会2013年度仙台大会　2013/03/24
5-Fluoro-2'-deoxyuridineの渦鞭毛藻Alexandrium tamarenseにおける麻痺性貝毒生合成初期中間体合成に与える影響

長由扶子, 土屋成輝, 大島泰克, 山下まり

日本農芸化学会2013年度仙台大会　2013/03/24
新規テトロドトキシン類縁体6-デオキシテトロドトキシンの単離・構造決定

工藤雄大, 長由扶子, 山下まり

日本農芸化学会2013年度仙台大会　2013/03/24
マイトトキシンの生理作用に影響を与える脂質および受容体の探索

ERATOタンパク質関連情報交換会　2012/11/26

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日時：11月26日(月), 15時～18時20分場所：大阪大学大学院理学研究科, E204講義室
Self-defence mechanism of diarrhetic shellfish poisoning toxins-accumulating species International-presentation

The 1st International Symposium on Chemical Biology of Natural Products: Target ID and Regulation of Bioactivity　2012/10/31
質量分析を用いたイチイ中のタキソール結合タンパク質の探索

工藤佑馬, 阿部晃大, 長由扶子, 山下まり

日本農芸化学会東北支部会第147回大会　2012/10/06
沖縄県阿嘉島産リングビアトキシン生産藍藻の16S rDNAの部分塩基配列

武田篤, 長由扶子, 佐久川さつき, 須田彰一郎, 山下まり

日本農芸化学会東北支部第147回大会　2012/10/06
HILIC-ESI-Q-TOF-MSを用いたテトロドトキシン類縁体の微量分析法の開発

工藤雄大, 長由扶子, 山下まり

日本農芸化学会東北支部第147回大会　2012/10/06
麻痺性貝毒生合成初期中間体の合成と毒生産生物からの同定

土屋成輝, 長由扶子, 長澤和夫, 大島泰克, 山下まり

第54回天然有機化合物討論会　2012/09/18
ホタテ貝中の下痢性貝毒変換酵素の探索

小野田竜也, 長由扶子, 加賀新之助, 渡邉龍一, 鈴木敏之, 山下まり

第59回毒素シンポジウム　2012/08/30
沖縄産シリケンイモリ(Cynops ensicauda popei)の新規テトロドトキシン類縁体の単離・構造決定、及びイモリとフグの毒組成比較

工藤雄大, 長由扶子, 安元健, 山下まり

日本農芸化学会2012年度大会　2012/03/22

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発表者：工藤雄大
海洋性カロテノイド、フコキサンチンのヒドロキシル基修飾体の細胞毒性とタンパク質結合体の作製

野村駿, 長由扶子, 山下まり

日本農芸化学会2012年度大会　2012/03/22

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発表者：野村駿
クロイソカイメン細胞の培養およびオカダ酸結合タンパク質OABP2.1の局在

小濱真実, 松浦宏樹, 西谷豪, 伊東久美子, 大和田修一, 長由扶子, 山下まり

日本農芸化学会2012年度大会　2012/03/22

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発表者：小濱真実
クロイソカイメン中のオカダ酸、オカダ酸結合タンパク質の定量および局在

松浦宏樹, 小濱真実, 福沢世傑, 橘和夫, 長由扶子, 山下まり

日本農芸化学会2012年度大会　2012/03/22

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発表者：松浦宏樹
紅藻からの新規プロスタグランジン代謝物の単離、構造決定とマウス組織中での同定

金井良和, 廣木禎彦, 越野広雪, 長由扶子, Cayme Mirriam, 福代康夫, 山下まり

日本農芸化学会2012年度大会　2012/03/22

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発表者：金井良和
Target candidate for maitotoxin, the most toxic marine natural product International-presentation

International ERATO Symposium on Lipid Structures in and around Proteins　2011/11/12
クロイソカイメンやダイダイイソカイメンの下痢性貝毒に対する耐性機構

第25回先端農学セミナー　2011/10/21
ホタテ貝(Patinopecten yessoensis)中のオカダ酸アシル化酵素の探索

小野田竜也, 渡邊龍一, 長由扶子, 鈴木敏之, 山下まり

日本農芸化学会東北支部第146回大会　2011/10/08

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発表者：小野田竜也
新規テトロドトキシン類縁体の同定と各種海洋生物中の毒組成の比較

阿部由佳, 西川俊夫, 磯部稔, 小野寺健一, 長由扶子, 安元健, 山下まり

日本農芸化学会東北支部第146回大会　2011/10/08

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発表者：阿部由佳
沖縄産シリケンイモリ(Cynops ensicauda popei)の新規テトロドトキシン類縁体の単離と構造決定

工藤雄大, 長由扶子, 安元健, 山下まり

第53回天然有機化合物討論会　2011/09/27

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発表者：工藤雄大
下痢性貝毒蓄積生物の自己耐性機構について

此木敬一

第6回化学生態学研究会　2011/06/17
オカダ酸結合タンパク質OABP2.1を生産する生物の探索

此木敬一, 小濱真実, 小野田竜也, 長由扶子, 山下まり

日本農芸化学会2011年度大会　2011/03/25

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東日本大震災のため本大会は実施されなかったが、大会は成立したことになった。
クロイソカイメン中のオカダ酸の生理機能

此木敬一, 松浦宏樹, 斎藤香, 長由扶子, 山下まり, 宮本智文, 杉山直幸, 福沢世傑, 橘和夫

第52回天然有機化合物討論会　2010/09/29

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ショートトークあり
天然毒貯蔵生物の耐性機構

此木敬一

第9回化学系薬学若手研究者セミナー　2010/09/04
マウス神経芽細胞腫(Neuro2A)に発現する電位依存性Na+チャネルサブタイプの解析と4,9-アンヒドロテトロドトキシンのNa+チャネル阻害活性

木村奏子, 此木敬一, 山下まり

第144回日本農芸化学会東北支部大会　2009/10/31
改良合成法を基盤とした（＋）－デカルバモイルサキシトキシンおよび（＋）－ゴニオトキシン3の全合成

岩本理, 篠原涼子, 此木敬一, 山下まり, 長澤和夫

第51回天然有機化合物討論会　2009/10/07
テトロドトキシンの蛋白質化体およびビオチン化体の作製と生化学的応用

山下まり, 金子陸, 山田京平, 山口日出起, 此木敬一

第51回天然有機化合物討論会　2009/10/07
クロイソカイメン由来の新規オカダ酸結合タンパク質の生理機能

此木敬一, 松浦宏樹, 斎藤香, 長由扶子, 山下まり

平成21年度化学系学協会東北大会　2009/09/19
有毒二次代謝産物を貯蔵する生物の自己耐性機構

研究室セミナー　2009/07/22

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九州大学大学院・薬学研究院・医薬資源探索学分野の宮本智文准教授より依頼を受け、講演を行った。
イオンチャネルに結合する有毒二次代謝産物－6年間のポスドク生活で学んだこと

第二回先端農学シンポジウム　2009/06/25
クロイソカイメンHalichondria okadai由来の新規オカダ酸結合タンパク質の生理機能

松浦宏樹, 斎藤香, 長由扶子, 山下まり

第6回東北大学バイオサイエンスシンポジウム　2009/06/16

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此木敬一は第二著者です。優秀ポスター賞候補になりました。
(+)-サキシトキシンの全合成およびその誘導体のナトリウムチャネル阻害活性評価

岩本理, 山下まり, 長澤和夫

第50回天然有機化合物討論会　2008/09/30

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此木敬一は第二著者です。主に山下まり教授が担当された細胞毒性試験の部分についてディスカッションを行いました。
Determination of the ladder-shaped polyether-binding dodecapepitdes from the phage display library International-presentation

Keiichi Konoki, Rie Tamate, Shiori Umemoto, Ryota Mouri, Futoshi Hasegawa, Kohei Torikai, Nobuaki Matsumori, Toru Oishi, Michio Murata

The 22nd Naito Conference on Chemical Biology　2008/09/09
Okadaic acid binding proteins from the sponge Halichondria okadai

Naoyuki Sugiyama, Keiichi Konoki, Kazuo Tachibana

Asia-Pacific Conference on Chemical Ecology 2007 Tsukuba　2007/09/10

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short talk and poster presentation
Identification of brevetoxin-binding sites on the voltage-dependent sodium channels. International-presentation

Keiichi Konoki, Todd Scheuer, William A. Catte

1st Asia International Symposiumin in Chemical Society of Japan Annual Meeting　2007/03/25
カナダ東部麻痺性貝毒蔓延域に生息するオオノガイが獲得した耐性機構

サントリー生物有機科学研究所内セミナー　2006/10/17

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財団法人サントリー生物有機化学研究所楠本正一所長
カナダ東部麻痺性貝毒蔓延地域に生息するオオノガイが獲得した耐性機構

V. Monica Bricelj, Laurie Connell, 此木敬一, Scott P. MacQuarrie, Todd Scheuer, William A. Catterall, Vera L. Trainer

第48回天然有機化合物討論会　2006/10/11
麻痺性貝毒サキシトキシンに耐性を示すオオノガイ由来ナトリウムチャネルの構造と機能に関する研究

京都大学化学研究所セミナー　2006/07/20

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京都大学化学研究所中村正治教授
麻痺性貝毒蔓延域に生息するオオノガイが獲得した耐性機構

第7回生命構造化学セミナー　2006/02/23

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東北大学大学院農学研究科佐々木誠教授
Sodium channel mutation responsible for saxitoxin resistance in clams increases risk of PSP International-presentation

V. Monica Bricelj, Laurie Connell, Keiichi Konoki, Scott P. MacQuarrie, Todd Scheuer, William A. Catterall, Vera L. Trainer

The 2nd Yamada Symposium on Key Natural Organic Molecules in Biological Systems　2005/09/10

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Short talk and poster presentation
Binding site for maitotoxin and brevetoxins. International-presentation

Keiichi Konoki, Michio Murata, Kazuo Tachibana, Takeshi Yasumoto

The 1995 International Chemical Congress of Pacific Basion Societies　1995/12
高純度テトロドトキシン類縁体の調製

山下まり, 佐藤恭佳, 工藤雄大, 長由扶子, 此木敬一

平成31年度公益社団法人日本水産学会春季大会

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Industrial Property Rights 1

オカダ酸に結合する新規タンパク質、およびその遺伝子

橘和夫, 此木敬一, 杉山直幸

Property Type: Patent

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http://www.j-tokkyo.com/2002/C12N/JP2002-101886.shtml

Research Projects 23

ホタテガイ等の麻痺性貝毒検査における機器分析導入に向けた標準物質製造技術の開発

Offer Organization: 農林水産省

System: 令和６年度農林水産研究の推進（委託プロジェクト研究）ホタテガイ等の麻痺性貝毒検査における機器分析導入に向けた標準物質製造技術の開発

2024/04 - 2027/03
下痢性貝毒の新規定量法の確立

Offer Organization: 三島海雲記念財団

System: 2023年度【自然科学部門】個人奨励金

2023/06 - 2025/03
マイトトキシンによる膜透過性亢進作用の完全解明

此木敬一

Offer Organization: 日本学術振興会

System: 科学研究費助成事業基盤研究(C)

Category: 基盤研究(C)

Institution: 東北大学

2022/04 - 2025/03
新規下痢性貝毒定量法の確立

Offer Organization: 国立大学法人東北大学産学連携機構スタートアップ事業化センター

System: 令和 4 年度第 1 回東北大学ビジネス・インキュベーション・プログラム

Institution: 東北大学

2022/06 - 2023/03
下痢性貝毒の新規定量法の確立

Offer Organization: 一般財団法人東洋水産財団

System: 学術奨励金

Institution: 東北大学

2022/06 - 2023/03
Design and synthesis of calcium ion regulatory molecules based on maitotoxin

Oishi Tohru

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (B)

Institution: Kyushu University

2019/04/01 - 2022/03/31

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Maitotoxin (MTX) is a ladder-shaped polyether isolated form the dinoflagellate Gambierdiscus toxicus. The molecular weight of MTX is 3422. MTX is a highly toxic compound against mammals, and it elicits potent calcium ion influx. MTX is an amphiphilic molecule comprised of hydrophobic and hydrophilic regions. As a part of the structure-activity relationship studies of MTX based on the chemical synthesis of partial structures of MTX, the WXYZA’B’C’ ring system was synthesized, and found that the hydrophobic region elicited inhibitory activity against calcium ion influx activity induced by MTX. In this study, more advanced partial structure, the WXYZA’B’C’D’E’F’ ring system (MW 1140) was synthesized based on the convergent method via alpha-cyano ethers developed by our group from the WXYZ and C’D’E’F’ ring systems. The NMR data of the synthetic specimen were in good agreement with those of the natural product, confirming the proposed structure.
Dynamic conformation and domain structure of lipid molecules in model biomembranes Competitive

Michio Murata

Offer Organization: Ministry of Education, Culture, Sports, Science and Technology

System: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

2017/06 - 2022/03
テトロドトキシンのリスク管理のための研究 Competitive

鈴木敏之

Offer Organization: 厚生労働省

System: 厚生労働科学研究費・食品の安全確保推進研究事業

2018/04 - 2021/03
各種疾病治療を目指した電位依存性ナトリウムチャネルサブタイプ選択的阻害剤の探索 Competitive

此木敬一

Offer Organization: 日本学術振興会

System: 科学研究費補助金・基盤研究 (B)

2017/04 - 2021/03
超活性天然物「マイトトキシン」の作用標的分子探索

Offer Organization: 公益財団法人上原記念生命科学財団

System: その他の競争的資金

Category: 研究助成

2020/01 - 2020/12
Elucidation of mode-of-action of maitotoxin based on chemical synthesis Competitive

Tohru Oishi

Offer Organization: Japan Society for the Promotion of Science

System: Grant-in-Aid for Scientific Research (B)

2016/04 - 2019/03
Molecular mechanisms of toxin synthesis in paralytic shellfish toxin producing dinoflagellates

Cho Yuko, YAMASHITA MARI, KONOKI KEIICHI

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2015/04/01 - 2018/03/31

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Saxitoxin and its analogues are potent neurotoxins which are named as paralytic shellfish toxins, collectively. The mechanism of their biosynthesis were investigated by the comparison of the toxic and non-toxic subclones of the dinoflagellate, Alexandrium tamarense. The analytical methods were developed for the expression analysis (the immunohistochemical method for the biosynthetic enzymes and the column switching HILIC-MS method for the biosynthetic intermediates). By these methods, the key steps toward the non-toxic mutation was suggested to be the first few steps in the complicated STX biosynthetic pathway. Moreover unexpectedly, the localization of the enzymes which catalize the first and the second step were suggested to be different. It leads us to the new hypothesis that there could be some unknown regulation mechanism other than the regulation of the protein expression.
Elucidation of biosynthetic pathways towards tetrodotoxin and saxitoxin based on the structures of novel biosynthetic intermediates

Yamashita Mari, NISHIKAWA TOSHIO, NAGASAWA KAZUO, KONOKI KEIICHI, CHO YUKO

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2014/04/01 - 2017/03/31

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We reported the first C10-C5 directly bonded tetrodotoxin (TTX) analogues from newts, and proposed monoterpene origin of TTX. In this study, five novel bicyclic guanidine compounds related to TTX were isolated and their structures were determined. These structures strongly supported monoterpene origin of TTX. Although biosynthetic genes corresponding to production of STX had been reported, chemical study of intermediates were not enough. In this study, Int-A', Int-C'2, and CyclicC' were chemically synthesized, and identified in toxin producing cyanobacterium and dinoflagellate using high resolution LC-MS/MS. In addition, incorporation experiments with 15N labeled these intermediates indicated that Int-A' and Int-C'2 are genuine precursors of STX analogues and Cyclic C' is a shunt compound. This is the first shunt pathway in STX biosynthesis ever found.
Preparation of the first antibody against carotenoids and elucidation of their target molecules in tissues and cells by visualization

Yamashita Mari, KONOKI KEIICHI, CHO YUKO

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2014/04/01 - 2016/03/31

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We prepared antibodies against carotenoids to quantify them and to elucidate their target molecules by visualization of them in tissues and cells. The anti-fucoxanthin and anti-retinoic acid antibodies were prepared by immunization of rabbits by their protein conjugates. These antibodies individually showed specific reactivities to fucoxanthin or retinoic acid. The localization of retinoic acid in mouse neuroblastoma cell line was visualized using this anti-retionoic acid antibody. Retinoic acid was specifically detected in cytoplasm by this antibody when the neuroblastoma cell was treated with retinoic acid to promote neurite outgrowth.
Synthesis and functional analysis of ion channel selective inhibitors based on polycyclic ethers

Sasaki Makoto, FUWA HARUHIKO, KONOKI KEIICHI

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Institution: Tohoku University

2011/04/01 - 2016/03/31

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Gambierol is a structurally complex marine polycyclic ether natural product that exhibits potent inhibitory activity against voltage-gated potassium ion channels (Kv channels) with specific subtype selectivity. In order to clarify skeletal structure-activity relationship, hepta-, tetra-, and tricyclic analogues of gambierol were synthesized and tested for inhibitory activity against Kv1.2 channel, which was stably expressed in Chinese hamster ovary (CHO) cells. It was revealed that tetracyclic analogue of gambierol comprising the right-hand EFGH-ring with a triene side chain is the minimal structural unit for inhibitory activity against Kv1.2 channels. Furthermore, we designed and synthesized photoaffinity probe based on the structure of the tetracyclic analogue to identify the binding site of the ligand on Kv channels.
Synthetic Studies of Maitotoxin to Elucidate Mode-of-Action Competitive

Tohru Oishi

Offer Organization: Japan Society for the Promotion of Science

System: Grant-in-Aid for Scientific Research (A)

2012/04 - 2016/03
Control of ion-channel functions by analogues of natural toxins Competitive

Toshio Nishikawa

Offer Organization: Ministry of Education, Culture, Sports, Science and Technology

System: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area): Chemical Biology using bioactive natural products as specific ligands: identification of molecular targets and regulation of bioactivity

2011/04 - 2016/03
Elucidation of mechanism for the non-toxic mutation of the paralytic shellfish toxin producing dinoflagellates by integrated omics analysis

CHO Yuko, HIDEMA Shizu, KONOKI Keiichi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2012/04/01 - 2015/03/31

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Alexandrium tamarense is one of the most popular marine dinoflagellates, which are causative for the paralytic shellfish poisoning in Japan. The metabolomics study on the toxic and non-toxic sub-clones of the dinoflagellate, A. tamarense, revealed that the putative intermediates of saxitoxin biosynthesis were not found in the non-toxic subclone. The low reactivity at the first stage was expected to be responsible for the loss of toxicity. The molecularbiological study using the toxic and non-toxic sub-clones was conducted on the basis of this hypothesis. SxtA4 gene, which is the putative saxitoxin biosynthesis gene assigned at the first stage, was observed in the genome and mRNA of the non-toxic sub-clone, however, they included mutation and its expression in the mRNA of the non-toxic sub-clone was extremely lower than that of the toxic sub-clone. The loss of toxicity was suggested to be related to the difference of sxtA4 gene.
Screening of an enzyme that transforms the diarrhetic shell fish poisoning toxins into 7-O-acylated derivative, from the Patinopecten yessoensis Competitive

Keiichi Konoki

Offer Organization: Japan Society for the Promotion of Science

System: Grant-in-Aid for Scientific Research (C)

2012/04 - 2015/03
Total Synthesis and Functional Analysis of Complex Natural Products Competitive

Makoto Sasaki

Offer Organization: Japan Society for the Promotion of Science

System: Grant-in-Aid for Scientific Research (A)

Category: Grant-in-Aid for Scientific Research (A)

Institution: Tohoku University

2009/04 - 2012/03

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Efficient synthetic routes to architecturally complex natural products with potent biological activities and molecular weights over 500 have been developed for exploring their biological functions. In particular, the first total synthesis and complete stereostructure determination of gambieric acid A have been accomplished. An efficient total synthesis of polycavernoside A has been also achieved in a convergent approach. In addition, efficient synthetic routes to the C1. C16 and C12. C36 fragments of goniodomin A have been developed by exploiting Stille-type coupling of thioesters.
Self-resistance mechanism for secondary metabolite-accumulating species-Structure and function of okadaic acid-binding proteins Competitive

Keiichi Konoki

Offer Organization: Japan Society for the Promotion of Science

System: Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2009/04 - 2012/03

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Okadaic acid binding proteins OABP_s 2. 1 and 2. 3, originally isolated from the sponge Halichondria okadai, were stably expressed as recombinant proteins in E. coli. Dissociation constants of OA from recombinant OABP_s 2. 1 and 2. 3 were determined in the binding assays. The okadaic acid binding proteins were deduced to be the sponge proteins but not those from symbiotic species. Furthermore, we quantitated okadaic acid and OABP2. 1 in the sponge collected from various places in Japan, and speculated a possible self-defense system of the sponge.
生体分子間相互作用解析装置を用いたオカダ酸結合タンパク質の同定 Competitive

此木敬一

Offer Organization: 日本学術振興会

System: 科学研究費補助金・奨励研究(A)

1998/04 - 2000/03
Molecular Mechanism of Action for Particularly Potent Marine Biotoxins.

MURATA Michio, SASAKI Makoto, TACHIBANA Kazuo, KONOKI Keiichi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (B).

1998 - 2000

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Maitotoxin (MTX) was first discovered as one of the toxins responsible for ciguatera, a seafood poisoning caused by ingestion of coral reef fish. MTX has extremely potent bioactivities ; its toxicity is particularly worth noting, since its LD_<50>(50 ng/kg, mouse ip.) is exceeded only by a few proteinaceous toxins. MTX elicits Ca^<2+> influx in virtually all cells and tissues and this elevation in intracellular calcium concentration leads to secondary events ; e.g., phosphoinositide breakdown, arachidonic acid release, muscle contraction, and secretion of dopamine, norepinephrine, and insulin. Gangliosides GM1 and GM3 strongly inhibited MTX-induced Ca^<2+> influx in C6 cells. Their inhibitory potency was in the order GM1 (IC_<50>, ca. 2 μM)>GM3 (ca. 5 μM)>asialo-GM1 (ca. 20 μM). GM1 (3 μM) completely blocked MTX(30 nM)-induced Ca^<2+> influx in human erythrocyte ghosts. When C6 cells were pretreated with tunicamycin, an antibiotic which inhibits N-linked glycosylation, or concanavalin A, a lectin which exhibits high affinity for cell-surface oligosaccharides, MTX-induced Ca^<2+> influx was significantly potentiated. This suggests that removal of oligosaccharides from the cell surface by tunicamycin or capping of sugar chains on plasma membranes by concanavalin A can potentiate the action of MTX.Photoaffinity labeling experiment to identify MTX-binding protein was carried out with use of a daizirine-biotin conjugated reagent developed by Hatanaka. Some spots on 2D electrophoresis, corresponding to 2 KDa were eliminated by addition of an MTX inhibitor, brevetoxin-B.

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Social Activities 7

東北大学MOOC講師及び講座企画運営委員

東北大学サイエンスシリーズ「海産毒の科学」

2024/04/01 - 2026/03/31
アグリビジネス創出フェア

2009/11/25 - 2009/11/27

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東北大学大学院農学研究科を代表して5研究室から展示ブースを１つ出し、アグリビジネス創出に関する研究成果の発表を行った。本研究者の展示ポスターの題目は「下痢性貝毒の微量検出法の開発」である。
第48回農学カルチャー講座

2015/02/21 -

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第48回農学カルチャー講座にご出演された講師でおられる藤井智幸先生のご講演内容が紹介された。
第７６回日本農芸化学会サイエンスカフェ・第４８回農学カルチャー講座

2015/02/21 -

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内容１：「食べ物を美味しくする油の役割」私たちが日常食べている食品の中には様々な脂質が含まれており、食品の風味、食感、栄養等の面で大切な役割を果たしています。油脂製品の代表といえば、サラダ油、バター、マーガリン、マヨネーズなどですが、食品の中には目に見えない状態で存在している油もあり、このような油もまた食感や美味しさに大きな影響を及ぼします。本講演では、油脂の基本的な性質に加え、マーガリン等の加工油脂製品がパン、菓子を作る過程でどのような働きをしているかについて考えてみたいと思います。また、実際に、違う種類の油脂を練りこんだパン、ビスケット等（未定）を食べていただき、油脂の違いが食感や風味に与える影響を実感して頂きたいと思います（お土産：家庭用マーガリン１個／人）内容２：「伝統食品に見る食べ物を美味しくする智慧−故きを温ねて新しきを知る−」新潟県北部の村上地方では、冬になると遡上した鮭
第７２回日本農芸化学会サイエンスカフェ・第４７回農学カルチャー講座

2014/11/15 -

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「食」は私たちが生物として生命を維持するために必須であるだけでなく、「人間」として豊かな生活を営むためにも重要なものであり、長い人類の歴史の中で様々な「食文化」が育まれてきました。しかし、科学の発展に伴う社会構造や経済情勢の変化により、私たちの「食生活」も激変し、生活習慣病が大きな問題となっています。さらに、原子力発電所の事故による放射線の影響など、私たちの「食」は新たな脅威にも曝され、「食」を「科学」する重要性がより一層高まっています。おいしいビール片手に最先端の「食の科学」を聴きながら、ほろ酔いで「食」と「安全・健康」について考えてみませんか？＜演題予定＞・物部真奈美（農業・食品産業技術総合研究機構）「お茶の防護効果」・宮澤陽夫（東北大学）「食と安全・健康」・小西豊（キリン株式会社）「プラズマ乳酸菌」
気仙沼高校東北大学体験会

2011/11/26 -

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気仙沼地域教育支援プロジェクトに付随して、本学環境科学研究科の浅沼宏司先生が企画された気仙沼高校東北大学体験会の一部を担当し、備考欄に記載した講義題目と実験題目に基づき、参加された高校生を教育指導した。
東北大学イノベーションフェア2009in仙台

2009/10/14 -

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「下痢性貝毒の微量検出法の開発」という題目でポスターの展示を行った。

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Other 12

クロイソカイメン中の共生生物の純化・培養－オカダ酸生産生物の同定

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【目的】軟体動物であるダイダイイソカイメンおよびクロイソカイメンに生息する共生生物を純化・培養し、オカダ酸を生産する共生生物を同定する。【研究代表者：此木敬一】神奈川県三浦市を中心とする関東以南の海岸地域を訪ね、クロイソカイメンおよびダイダイイソカイメンをサンプリングする。サンプリングは大潮時の潮位が比較的低くなる3月下旬から9月上旬にかけて実施する。EDTA処理により解離したカイメン細胞および共生生物の混合顕濁液を二分する（画分1、2）。画分1を孔径の異なるナイロンメッシュ（10, 25, 40, 77, 100 µm）により分画し、LC-MS/MSにより各画分のOAの含有量をもとめる。対照実験としてダイダイイソカイメンを同様に処理する。OA含有量の最も高かったクロイソカイメン由来の画分に含まれる生物種を同定し、そのオカダ酸生産能を確認する。本研究費はサンプリングに行くための旅行費、顕微鏡観察やLC-MS/MS測定に必要な消耗品に充てる予定である。【共同研究者：西谷豪】画分2に多数共生している珪藻、渦鞭毛藻、多毛類などを1細胞ずつピックアップし，形態観察および遺伝子解析を行って種を同定する。また、クロイソカイメンの採取海域や採取時期の違いによって，共生生物の多様性がどのように変化していくのか追跡する。本研究費より遺伝子クローニングや配列解析に必要な試薬類、ディスポーザブル実験器具等を購入する予定である。
海洋天然物の生理活性発現機構の解明

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海洋天然物の生理活性発現機構の解明を行うが、詳細は述べられない
下痢性貝毒蓄積生物における自己耐性機構の解明

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下痢性貝毒蓄積生物における自己耐性機構の解明を行う、詳細はまだ述べられない
天然毒貯蔵生物がもつ自己耐性機構

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強力な毒性を示す天然毒は、医薬品開発における鍵化合物、または有用な細胞生理研究試薬となる。しかし、二次代謝産物である「天然毒の自然環境下、例えば、生産・貯蔵する生物の体内での機能」については、ほとんど研究成果が得られておらず、未開拓研究領域と言える。軟体動物のカイメン類から種々の強力な毒性をもった天然毒が単離されてきた。研究代表者は天然毒と真の生産者と宿主カイメンとの共生関係において、カイメンは天然毒に対する「免疫＝耐性」をもつと考えている。本研究ではこの仮説を証明するため、オカダ酸および研究代表者がクロイソカイメンから見出したOABP1に注目し、オカダ酸貯蔵生物種がオカダ酸を貯蔵できる化学的根拠を明らかにする。
ファージディスプレーライブラリーを用いる梯子状ポリエーテル結合性ドデカペプチドの探索

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ビオチン基を導入した梯子状ポリエーテルを合成し、ストレプトアビジン固定化ゲルに捕獲した。NEB社製Ph.D.-12 Phage Display Library Kitを用い、梯子状ポリエーテルに結合性を示すファージを抽出し、外部挿入配列を決定した。
ギンコライドおよびタキソールが結合性を示す内在性受容体の同定

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イチイ、イチョウ由来の二次代謝産物タキソール、ギンコライドについて、各植物内における内在性受容体を同定する。イチイやイチョウのように臨床薬あるいは基礎研究試薬として重要な二次代謝産物を生産または貯蔵する生物は数多く知られているが、その理由は不明である。二次代謝産物の結合の痕跡を調べるTRAFFIC法を考案し、誰もが不思議に思う自然界の摂理に挑み、二次代謝産物の真の機能を解明する手掛かりを得たいと考えている。
医薬・農薬リード開発を指向した海洋及び植物起源生理活性物質の合成とその機能解明に向けた新手法の開発

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作物病害や食品中毒、感染症など、人間の安定な生活を脅かす様々なマクロな生命現象の多くには、化学物質のミクロな相互作用が重要な働きを果たしている。これら分子間の化学的な働きを解明し、応用することは、生物的災害の防除のために必須である。また、様々な生命現象に関わる有機低分子物質は、未解明生命現象を解明するための鍵化合物であるとともに、農薬・医薬品開発におけるリード化合物として産業上も重要である。そして何れの場合も、鍵低分子化合物と受容体高分子との相互作用が機能発現の引き金であり、その受容体高分子を探索・同定することが必要不可欠である。しかしながら、天然からの物質資源の供給量が限られていること、受容体同定を可能にする統一的方法論が開発されていないことが問題となっている。本研究では未解明生命現象の解明とそれに基づく農薬・医薬品開発を目的とし、海洋・植物起源の様々な生物活性物質に焦点を当て、総合的な生物科学研究を行う。
Structure and Activity Relationship of Neopeltolide

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ネオペルトリドは深海に棲息するNeopeltidae科海綿より単離されたマクロリド天然物であり、A-549ヒト肺線がん細胞、NCI-ADR-RES卵巣肉腫細胞、P388マウス白血病細胞に対して非常に強力な細胞毒性を示し、また病原性真菌Candida albicansに対して生育阻害活性を示す。本研究では、ネオペルトリドの構造活性相関の解明を目的として、マウス白血病細胞P388細胞を用いた細胞毒性試験を実施する。
電位依存性ナトリウムチャネル上における赤潮毒ブレベトキシン結合部位の同定研究

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赤潮毒ブレベトキシンは電位依存性ナトリウムチャネルに結合して機能を改変する神経毒である。すでに光親和性標識実験が行われておりドメイン1セグメント6、ドメイン4セグメント5に結合部位が存在することが示唆されている。本研究では両セグメントのほか近隣のセグメントについてアラニンスキャンを行いブレベトキシンとの高親和性結合に寄与するアミノ酸の決定を行った。
各種神経疾患に対する治療薬候補の提供を目的とする電位依存性Na+チャネルサブタイプ選択的阻害剤の探索（１）

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フグ毒として知られるテトロドトキシン（Tetrodotoxin, TTX）はNav阻害剤であるが、Nav1.5、1.8、1.9はTTX非感受性です。サブタイプ間で一次構造が高く保存されているNaV1型ですが、僅かな構造の違いがもたらす劇的な結合性の変化は起こりうると私は考えます。TTX類縁体は海洋、陸上に生息する多数の生物より見出されていますが、TTX以外、各Navサブタイプに対する結合性は調べられていませんでした。私達は、名古屋大学の西川俊夫教授と共同でTTXと11種類のTTX類縁体、また、TTX同様、グアニジン
イオンチャネルなど膜タンパク質の機能評価に関する研究

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電位依存性イオンチャネルは、神経、脳、心筋、骨格筋などの組織で細胞膜に発現するタンパク質であり、神経興奮作用の基盤をつくりだす重要な役割を担う。遺伝学的にもっとも原始的であるK+チャネルの中で、いくつかの型の高次構造はX線構造解析により明らかにされている。しかし、同解析に適した試料の調製が困難であるNa+チャネル、Ca2+チャネルの高次構造や開閉機構の実態は、薬理実験や電気生理実験を積み重ね、より高精度に推測していかなければならない。こうした古典的手法を適用する際、特異的な結合阻害剤を用いた方法論は現在でも有効である。通称、「梯子状ポリエーテル」と呼ばれる化合物群は、環状エーテルが連結する特徴的な共通構造を有するものの、その生理活性は多岐にわたる。しかし、その多くがイオンチャンルを標的にすることがわかってきている。合成化学者の功績により試料供給がなされた化合物については作用研究が進展しており、例えば、シガトキシン類はNa+チャネルの特定の型に、ガンビエロールはK+チャネルの特定の型に結合することが明らかになった。一方、マイトトキシンはマウス急性致死毒性の強さで二次代謝産物中、最強の化合物であることが知られているが、その標的分子は不明である。2009年、Sinkinsらはマイトトキシンの標的分子がCa2+ -ATPaseであることを報告したが、追試および追求の余地が残されている。本研究では、（１）マイトトキシンの作用標的解明に向けた受容体探索を行うことを第一の目的とする。このために、①赤血球膜より再構成させた脂質二重膜、②単離・精製した膜タンパク質を再構成させた脂質二重膜、③イオンチャネルを一過的もしくは安定的に高発現させた培養細胞を調製し、電気生理実験によりマイトトキシンの生理作用を観察する予定である。また、（２）佐々木研究室で合成予定の化合物、すなわち、分子内にF原子を導入したガンビエロール誘導体の活性試験を行うことを目的とする。この目的のため、電依存性K+チャネルを安定的に高発現させた培養細胞を調製し、電気生理実験を実施する予定である。
各種神経疾患に対する治療薬候補の提供を目的とする電位依存性Na+チャネルサブタイプ選択的阻害剤の探索

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quality of lifeを低下させる「慢性疼痛」に悩む患者は極めて多い。その原因は多岐にわたり、長期間の投薬を必要とするため、その治療薬は三大疾患や糖尿病などの治療薬と同程度の市場規模を持つと推定される。「慢性疼痛」はブルガダ症候群やQT延長症候群などの病名で知られる「不整脈」や全般癲癇熱性けいれんプラスの病名で知られる「癲癇」と共に興奮性細胞の細胞膜に発現する電位依存性ナトリウムチャネル（Nav）に一部の原因が見出されており、Navは創薬研究上、重要な標的と言える1-5。9つのサブタイプから構成されるNav1型は様々な臓器で発現しているが、必ずしも臓器ごとに特定のサブタイプが単独で存在するわけではない。実際にNav1型を標的とし各種疾患に処方される治療薬はサブタイプ選択性に乏しく、必然的に副作用を伴うことになる。従って、より優れた治療薬の開発に向けて、サブタイプ選択的なNav1型阻害剤の探索は必須である。痛みは、末梢神経に存在し、機械刺激、化学刺激、熱、炎症等の各種刺激に応じる特定の侵害受容器が活性化され、これを契機に発生する活動電位が中枢神経に伝わることにより感じられる。この痛みシグナルに対するNavの関与は無痛症患者、肢端紅痛症患者のゲノム解析において明らかにされ、いずれもNav1.7遺伝子の改変に原因があるとされた。慢性疼痛は外傷（急性疼痛）に端を発し、当該外傷の治癒期間を経過した後も継続する痛みであり、その原因追求は困難とされる。急性疼痛と同様、後根神経節に発現し痛みシグナルを伝搬する役割を果たすNav1.7-1.9の各サブタイプは創薬研究上、重要視されているが、優れた治療薬となりうる選択的阻害剤は見出されていない2,3。一方、心臓疾患の一種である「不整脈」に対してNaV1.5遺伝子の改変が確認されている。心筋には主にNav1.5が発現するが、その他サブタイプの発現も報告されるようになり、「不整脈」の治療に際し、サブタイプ選択性を示さない現存の治療薬は副作用をもたらすことがわかっている。フグ毒として知られるテトロドトキシン（Tetrodotoxin, TTX）はNav阻害剤であるが、Nav1.5、1.8、1.9はTTX非感受性である。サブタイプ間で一次構造が高く保存されているNaV1型であるが、僅かな構造の違いがもたらす劇的な結合性の変化は起こりうる。TTX類縁体は海洋、陸上に生息する多数の生物より見出されているが、各Navサブタイプに対する結合性は調べられていない。また、有毒二次代謝産物の宝庫である軟体動物のカイメンに対してメタゲノム解析が盛んに行われていると推測するが、有毒二次代謝産物の生合成遺伝子群の同定やその再構築に対する難易度は極めて高い。そこで、古典的であるが可能な限り多数の共生微生物の純化を達成し、その培養抽出

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