Details of the Researcher

PHOTO

Kazumitsu Onizuka
Section
Institute of Multidisciplinary Research for Advanced Materials
Job title
Associate Professor
Degree

  • 博士（薬学）（九州大学）

  • 修士（薬学）（九州大学）

Professional Memberships 6

  • JAPANESE SOCIETY FOR CHEMICAL BIOLOGY

  • NUCLEIC ACIDS THERAPEUTICS SOCIETY OF JAPAN

  • THE SOCIETY OF SYNTHETIC ORGANIC CHEMISTRY, JAPAN

  • THE JAPAN SOCIETY OF NUCLEIC ACIDS CHEMISTRY

  • THE CHEMICAL SOCIETY OF JAPAN

  • THE PHARMACEUTICAL SOCIETY OF JAPAN

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Research Areas 3

  • Life sciences / Bioorganic chemistry /

  • Nanotechnology/Materials / Chemical biology /

  • Life sciences / Pharmaceuticals - chemistry and drug development /

Papers 55

  1. Generation of abasic sites in DNA by singlet oxygen produced from a photocatalytic reaction

    Yuuhei Yamano, Kazumitsu Onizuka, Okan Altan, Madoka Sasaki, Ahmed Mostafa Abdelhady, Fumi Nagatsugi

    2024/12/12

    DOI： 10.26434/chemrxiv-2024-7m8fx 　

  2. Crystallographic analysis of G-clamp–RNA complex assisted by large scale RNA-binding profile Peer-reviewed

    Ryosuke Nagasawa, Kazumitsu Onizuka, Karen Kawamura, Kosuke Tsuzuki, Hirotaka Murase, Kaoru R. Komatsu, Emi Miyashita, Hirohide Saito, Jiro Kondo, Fumi Nagatsugi

    Chemical Communications　61　1120-1123　2024/12

    DOI： 10.1039/D4CC04677C 　

  3. Photocatalytic proximity labeling for the identification of G-quadruplex DNA-interacting proteins

    Ahmed Mostafa Abdelhady, Shinichi Sato, Tatsuki Masuzawa, Keishi Deguchi, Keita Nakane, Zhengyi Liu, Kazuki Kuwahara, Fumi Nagatsugi, Takanori Oyoshi, Kazumitsu Onizuka

    2024/09/03

    DOI： 10.26434/chemrxiv-2024-909gq 　

  4. Michael addition-activated alkylation of G-quadruplex DNA with methylamine-protected vinyl-quinazolinone derivatives. International-journal

    Yutong Chen, Kazumitsu Onizuka, Fumi Nagatsugi

    Bioorganic & medicinal chemistry letters　109　129855-129855　2024/09/01

    DOI： 10.1016/j.bmcl.2024.129855 　

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    The role of G-quadruplex (G4) in cellular processes can be investigated by the covalent modification of G4-DNA using alkylating reagents. Controllable alkylating reagents activated by external stimuli can react elegantly and selectively. Herein, we report a chemical activation system that can significantly boost the reaction rate of methylamine-protected vinyl-quinazolinone (VQ) derivative for the alkylation of G4-DNA. The two screened activators can transform low-reactive VQ-NHR' to highly reactive intermediates following the Michael addition mechanism. This approach expands the toolbox of activable G4 alkylating reagents.

  5. Uracil‐selective Cross‐linking in RNA and Inhibition of miRNA Function by 2‐Amino‐6‐vinyl‐7‐deazapurine Deoxynucleosides International-journal

    Nadya Soemawisastra, Hidenori Okamura, Ahmed Mostafa Abdelhady, Kazumitsu Onizuka, Mamiko Ozawa, Fumi Nagatsugi

    ChemBioChem　e202400417　2024/06/24

    Publisher: Wiley

    DOI： 10.1002/cbic.202400417 　

    ISSN： 1439-4227

    eISSN： 1439-7633

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    MicroRNAs (miRNAs) regulate gene expression through RNA interference. Consequently, miRNA inhibitors, such as anti‐miRNA oligonucleotides (AMOs), have attracted attention for treating miRNA overexpression. To achieve efficient inhibition, we developed 2‐amino‐6‐vinylpurine (AVP) nucleosides that form covalent bonds with uridine counterparts in RNA. We demonstrated that mRNA cross‐linked with AVP‐conjugated antisense oligonucleotides with AVP were protected from gene silencing by exogenous miRNA. However, endogenous miRNA function could not be inhibited in cells, probably because of slow cross‐linking kinetics. We recently developed ADpVP, an AVP derivative bearing a 7‐propynyl group—which boasts faster reaction rate than the original AVP. Here, we synthesized dADpVP—a deoxy analog of ADpVP—through a simplified synthesis protocol. Evaluation of the cross‐linking reaction revealed that the reaction kinetics of dADpVP were comparable to those of ADpVP. In addition, structural analysis of the cross‐linked adduct discovered N3 linkage against uridine. Incorporating dADpVP into two types of miRNA inhibitors revealed a marginal impact on AMO efficacy yet improved the performance of target site blockers. These results indicate the potential of cross‐linking nucleosides for indirect miRNA function inhibition.

  6. Large-scale analysis of small molecule-RNA interactions using multiplexed RNA structure libraries Peer-reviewed

    Ryosuke Nagasawa, Kazumitsu Onizuka, Kaoru R. Komatsu, Emi Miyashita, Hirotaka Murase, Kanna Ojima, Shunya Ishikawa, Mamiko Ozawa, Hirohide Saito, Fumi Nagatsugi

    Communications Chemistry　2024/05/01

    DOI： 10.1038/s42004-024-01181-8 　

  7. Guanidine modification improves functions of natural RNA-targeting alkaloids Peer-reviewed

    Tamaki Endoh, Sagar Satpathi, Yutong Chen, Saki Matsumoto, Tatsuya Ohyama, Peter Podbevšek, Janez Plavec, Kazumitsu Onizuka, Fumi Nagatsugi, Naoki Sugimoto

    New Journal of Chemistry　48　(19)　8529-8533　2024/04

    Publisher: Royal Society of Chemistry (RSC)

    DOI： 10.1039/d3nj05833f 　

    ISSN： 1144-0546

    eISSN： 1369-9261

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    Guanidine modification on berberine improved RNA binding affinity and enhanced suppression of protein expression.

  8. Topological capture of mRNA for silencing gene expression. International-journal Peer-reviewed

    Fangjie Lyu, Takashi Tomita, Naoko Abe, Haruka Hiraoka, Fumitaka Hashiya, Yuko Nakashima, Shiryu Kajihara, Fumiaki Tomoike, Zhaoma Shu, Kazumitsu Onizuka, Yasuaki Kimura, Hiroshi Abe

    Chemical communications (Cambridge, England)　59　(77)　11564-11567　2023/09/26

    DOI： 10.1039/d2cc06189a 　

    ISSN： 1359-7345

    eISSN： 1364-548X

  9. Creation of unique nucleic acid structures using nucleic acid reaction fields Peer-reviewed

    Kazumitsu Onizuka

    Journal of Synthetic Organic Chemistry, Japan　81　(8)　809-816　2023/08/01

    Publisher: The Society of Synthetic Organic Chemistry, Japan

    DOI： 10.5059/yukigoseikyokaishi.81.809 　

    ISSN： 0037-9980

    eISSN： 1883-6526

  10. Formation of Direction-Controllable Pseudorotaxane and Catenane Using Chemically Cyclized Oligodeoxynucleotides and Their Noncovalent RNA Labeling Peer-reviewed

    Kazuki Kuwahara, Sayaka Yajima, Yuuhei Yamano, Fumi Nagatsugi, Kazumitsu Onizuka

    Bioconjugate Chemistry　2023/03/17

    Publisher: American Chemical Society (ACS)

    DOI： 10.1021/acs.bioconjchem.3c00031 　

    ISSN： 1043-1802

    eISSN： 1520-4812

  11. Reactivity Modulation of Reactive OFF–ON Type G-Quadruplex Alkylating Agents Peer-reviewed

    Yutong Chen, Kazumitsu Onizuka, Madoka E. Hazemi, Fumi Nagatsugi

    Bioconjugate Chemistry　33　(11)　2097-2102　2022/11/16

    Publisher: American Chemical Society (ACS)

    DOI： 10.1021/acs.bioconjchem.2c00458 　

    ISSN： 1043-1802

    eISSN： 1520-4812

  12. Photochemical Labeling of Nucleic Acid by Photocatalyst Tethered DNA Probe Peer-reviewed

    Yuuhei Yamano, Kazumitsu Onizuka, Madoka Sasaki, Shinichi Sato, Fumi Nagatsugi

    Chemistry Letters　51　(12)　1121-1124　2022/10/21

    Publisher: The Chemical Society of Japan

    DOI： 10.1246/cl.220397 　

    ISSN： 0366-7022

    eISSN： 1348-0715

  13. Selective Chemical Modification to the Higher-Order Structures of Nucleic Acids. International-journal Peer-reviewed

    Fumi Nagatsugi, Kazumitsu Onizuka

    Chemical record (New York, N.Y.)　e202200194　2022/09/16

    DOI： 10.1002/tcr.202200194 　

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    DNA and RNA can adopt a variety of stable higher-order structural motifs, including G-quadruplex (G4 s), mismatches, and bulges. Many of these secondary structures are closely related to the regulation of gene expression. Therefore, the higher-order structure of nucleic acids is one of the candidate therapeutic targets, and the development of binding molecules targeting the higher-order structure of nucleic acids has been pursued vigorously. Furthermore, as one of the methodologies for detecting the higher-order structures of these nucleic acids, developing techniques for the selective chemical modification of the higher-order structures of nucleic acids is also underway. In this personal account, we focus on the following higher-order structures of nucleic acids, double-stranded DNA containing the abasic site, T-T/U-U mismatch structure, and G-quadruplex structure, and describe the development of molecules that bind to and chemically modify these structures.

  14. Hybridization-specific chemical reactions to create interstrand crosslinking and threaded structures of nucleic acids. International-journal Peer-reviewed

    Kazumitsu Onizuka, Yuuhei Yamano, Ahmed Mostafa Abdelhady, Fumi Nagatsugi

    Organic & Biomolecular Chemistry　20　(23)　4699-4708　2022/06/15

    DOI： 10.1039/d2ob00551d 　

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    The interstrand crosslinking and threaded structures of nucleic acids have high potential in oligonucleotide therapeutics, chemical biology, and nanotechnology. For example, properly designed crosslinking structures provide high activity and nuclease resistance for anti-miRNAs. The noncovalent labeling and modification by the threaded structures are useful as new chemical biology tools. Photoreversible crosslinking creates smart materials, such as reversible photoresponsive gels and DNA origami objects. This review introduces the creation of interstrand crosslinking and threaded structures, such as catenanes and rotaxanes, based on hybridization-specific chemical reactions and their functions and perspectives.

  15. Synthesis of Crosslinked 2′‐OMe RNA Duplexes Using 2‐Amino‐6‐Vinylpurine and Their Application for Effective Inhibition of miRNA Function International-journal Invited Peer-reviewed

    Ahmed Mostafa Abdelhady, Yu Hirano, Kazumitsu Onizuka, Hidenori Okamura, Yasuo Komatsu, Fumi Nagatsugi

    Current Protocols　2　(3)　e386　2022/03

    Publisher: Wiley

    DOI： 10.1002/cpz1.386 　

    ISSN： 2691-1299

    eISSN： 2691-1299

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    Crosslinking reactions to nucleic acids are an effective way to prepare stable complexes formed by covalent bonding. We demonstrated that fully 2'-O-methylated (2'-OMe) RNAs having a 2-amino-6-vinylpurine (AVP) exhibited an efficient crosslinking to uracil in the target RNA. Recently, we reported the preparation of crosslinked 2'-OMe RNA duplexes using AVP and the anti-miRNA oligonucleotides (AMOs) containing crosslinked duplexes at the terminal positions. These AMOs exhibited efficient microRNA (miRNA) inhibition at very low concentrations. In this article, we describe the chemical synthesis of 2'-OMe oligonucleotides containing AVP and preparation of the AMOs bearing crosslinked 2'-OMe RNA duplexes using AVP. In addition, we describe in detail the miRNA inhibition assay using these AMOs. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Synthesis of phosphoramidite of 2-amino-6-vinylguanosine derivative Basic Protocol 2: Synthesis of AVP-2'-OMe RNA Basic Protocol 3: Evaluation of the crosslink reactivity of CFO containing AVP to the 2'-OMe RNA and preparation of AMOs containing crosslinked duplex Basic Protocol 4: miRNA inhibition assays.

  16. Rapid Alkene–Alkene Photo-Cross-Linking on the Base-Flipping-Out Field in Duplex DNA Peer-reviewed

    Ahmed Mostafa Abdelhady, Kazumitsu Onizuka, Kei Ishida, Sayaka Yajima, Eriko Mano, Fumi Nagatsugi

    The Journal of Organic Chemistry　2022/01/02

    Publisher: American Chemical Society (ACS)

    DOI： 10.1021/acs.joc.1c01498 　

    ISSN： 0022-3263

    eISSN： 1520-6904

  17. Synthesis of crosslinked 2 '-OMe RNA duplexes and their application for effective inhibition of miRNA function Peer-reviewed

    Ahmed Mostafa Abdelhady, Yu Hirano, Kazumitsu Onizuka, Hidenori Okamura, Yasuo Komatsu, Fumi Nagatsugi

    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS　48　2021/09

    DOI： 10.1016/j.bmcl.2021.128257 　

    ISSN： 0960-894X

    eISSN： 1464-3405

  18. Crosstalk between repair pathways elicits double-strand breaks in alkylated DNA and implications for the action of temozolomide Peer-reviewed

    Robert P. Fuchs, Asako Isogawa, Joao A. Paulo, Kazumitsu Onizuka, Tatsuro Takahashi, Ravindra Amunugama, Julien P. Duxin, Shingo Fujii

    ELIFE　10　2021/07

    DOI： 10.7554/eLife.69544 　

    ISSN： 2050-084X

  19. Selective alkylation of parallel G-quadruplex structure Peer-reviewed

    Kazumitsu Onizuka, Erchissaran Ganbold, Yue Ma, Shogo Sasaki, Madoka E. Hazemi, Yutong Chen, Norihiro Sato, Mamiko Ozawa, Kazuo Nagasawa, Fumi Nagatsugi

    Organic and Biomolecular Chemistry　19　(13)　2891-2894　2021/04

    DOI： 10.1039/d0ob02365e 　

    ISSN： 1477-0520

  20. Functional G-quadruplex binding molecules Peer-reviewed

    Fumi Nagatsugi, Kazumitsu Onizuka

    Chemistry Letters　49　(7)　771-780　2020/07

    DOI： 10.1246/cl.200214 　

    ISSN： 0366-7022

    eISSN： 1348-0715

  21. Reactive OFF-ON type alkylating agents for higher-ordered structures of nucleic acids Peer-reviewed

    Kazumitsu Onizuka, Madoka E Hazemi, Norihiro Sato, Gen-ichiro Tsuji, Shunya Ishikawa, Mamiko Ozawa, Kousuke Tanno, Ken Yamada, Fumi Nagatsugi

    Nucleic Acids Research　47　(13)　6578-6589　2019/06/12

    DOI： 10.1093/nar/gkz512 　

    ISSN： 0305-1048

    eISSN： 1362-4962

  22. Alkyne–Alkyne Photo-cross-linking on the Flipping-out Field Peer-reviewed

    Kazumitsu Onizuka, Kei Ishida, Eriko Mano, Fumi Nagatsugi

    Organic Letters　21　(8)　2833-2837　2019/04/19

    DOI： 10.1021/acs.orglett.9b00817 　

    ISSN： 1523-7060

  23. Structural optimization of pseudorotaxane-forming oligonucleotides for efficient and stable complex formation. International-journal Peer-reviewed

    Onizuka K, Miyashita T, Chikuni T, Ozawa M, Abe H, Nagatsugi F

    Nucleic acids research　46　(17)　8710-8719　2018/09

    DOI： 10.1093/nar/gky744 　

    ISSN： 0305-1048

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    Interlocked structures, such as rotaxane and catenane, combine both static and dynamic properties. To expand their unique properties into the chemical biology field, a spontaneous formation method of the interlocked structures with the target would be ideal. We have previously developed a pseudorotaxane-forming oligo DNA (prfODN) to spontaneously form topological DNA/RNA architectures. In this study, we report the structural optimization of prfODNs for the efficient and stable complex formation. The optimized prfODNs efficiently formed pseudorotaxane structures with a DNA or RNA target, and the yield for the RNA target reached 85% in 5 min. In addition, the optimized prfODNs could form the pseudorotaxane structure with a smaller ring size and the structure significantly increased the kinetic stability. Furthermore, the catenane structure was successfully formed with the optimized prfODNs to provide the conclusive evidence for the formation of the threaded structure. This information will be valuable for developing new chemical methods using functional nucleic acids for antisense oligo nucleotides and DNA/RNA nanotechnology.

  24. Vinyldiaminotriazine-acridine conjugate as G-quadruplex alkylating agent Peer-reviewed

    Madoka E. Hazemi, Kazumitsu Onizuka, Tomohito Kobayashi, Akira Usami, Norihiro Sato, Fumi Nagatsugi

    Bioorganic and Medicinal Chemistry　26　(12)　3551-3558　2018/07/23

    DOI： 10.1016/j.bmc.2018.05.030 　

    ISSN： 1464-3391 0968-0896

  25. Alkylating probes for the G-quadruplex structure and evaluation of the properties of the alkylated G-quadruplex DNA. International-journal Peer-reviewed

    Norihiro Sato, Shuntaro Takahashi, Hisae Tateishi-Karimata, Madoka E Hazemi, Tomoko Chikuni, Kazumitsu Onizuka, Naoki Sugimoto, Fumi Nagatsugi

    Organic & biomolecular chemistry　16　(9)　1436-1441　2018/02/28

    DOI： 10.1039/c7ob03179c 　

    ISSN： 1477-0520

  26. Selective alkylation of T-T mismatched DNA using vinyldiaminotriazine-acridine conjugate Peer-reviewed

    Kazumitsu Onizuka, Akira Usami, Yudai Yamaoki, Tomohito Kobayashi, Madoka E. Hazemi, Tomoko Chikuni, Norihiro Sato, Kaname Sasaki, Masato Katahira, Fumi Nagatsugi

    Nucleic Acids Research　46　(3)　1059-1068　2018/02/16

    DOI： 10.1093/nar/gkx1278 　

    ISSN： 1362-4962 0305-1048

  27. Pseudorotaxane formation via the slippage process with chemically cyclized oligonucleotides Peer-reviewed

    Kazumitsu Onizuka, Tomoko Chikuni, Takuya Amemiya, Takuya Miyashita, Kyoko Onizuka, Hiroshi Abe, Fumi Nagatsugi

    NUCLEIC ACIDS RESEARCH　45　(9)　5036-5047　2017/05

    DOI： 10.1093/nar/gkx265 　

    ISSN： 0305-1048

    eISSN： 1362-4962

  28. Synthesis of native-like crosslinked duplex RNA and study of its properties Peer-reviewed

    Kazumitsu Onizuka, Madoka E. Hazemi, Justin M. Thomas, Leanna R. Monteleone, Ken Yamada, Shuhei Imoto, Peter A. Beal, Fumi Nagatsugi

    BIOORGANIC & MEDICINAL CHEMISTRY　25　(7)　2191-2199　2017/04

    DOI： 10.1016/j.bmc.2017.02.034 　

    ISSN： 0968-0896

    eISSN： 1464-3391

  29. Synthesis and properties of cross-linkable DNA duplex using 4-amino-2-oxo-6-vinyl-1,3,5-triazine Peer-reviewed

    Ken Yamada, Shogo Ishiyama, Kazumitsu Onizuka, Fumi Nagatsugi

    TETRAHEDRON　73　(11)　1424-1435　2017/03

    DOI： 10.1016/j.tet.2017.01.043 　

    ISSN： 0040-4020

  30. Guide Strand 3 '-End Modifications Regulate siRNA Specificity Peer-reviewed

    Rachel A. P. Valenzuela, Kazumitsu Onizuka, Alexi A. Ball-Jones, Tiannan Hu, Scott R. Suter, Peter A. Beal

    CHEMBIOCHEM　17　(24)　2340-2345　2016/12

    DOI： 10.1002/cbic.201600453 　

    ISSN： 1439-4227

    eISSN： 1439-7633

  31. Efficient Thymidine-Selective DNA Interstrand Photo-activated Crosslinking by the 6-Thioguanine Connected via an Ethylene-Linker to the 2 '-Deoxyribose Unit Peer-reviewed

    Takamasa Nishioka, Ikuya Oshiro, Kazumitsu Onizuka, Yosuke Taniguchi, Shigeki Sasaki

    CHEMICAL & PHARMACEUTICAL BULLETIN　64　(9)　1315-1320　2016/09

    DOI： 10.1248/cpb.c16-00310 　

    ISSN： 0009-2363

  32. Structure-Guided Control of siRNA Off-Target Effects Peer-reviewed

    Scott R. Suter, Jessica Sheu-Gruttadauria, Nicole T. Schirle, Rachel Valenzuela, Alexi A. Ball-Jones, Kazumitsu Onizuka, Ian J. MacRae, Peter A. Beal

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY　138　(28)　8667-8669　2016/07

    DOI： 10.1021/jacs.6b06137 　

    ISSN： 0002-7863

  33. Stabilization of the i-motif structure by the intra-strand cross-link formation Peer-reviewed

    Kenji Kikuta, Haishun Piao, John Brazier, Yosuke Taniguchi, Kazumitsu Onizuka, Fumi Nagatsugi, Shigeki Sasaki

    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS　25　(16)　3307-3310　2015/08

    DOI： 10.1016/j.bmcl.2015.05.064 　

    ISSN： 0960-894X

    eISSN： 1464-3405

  34. Site-Specific Modification of the 6-Amino Group of Adenosine in RNA by an Interstrand Functionality-Transfer Reaction With an S-Functionalized 4-Thiothymidine Peer-reviewed

    Ikuya Oshiro, Daichi Jitsuzaki, Kazumitsu Onizuka, Atsushi Nishimoto, Yosuke Taniguchi, Shigeki Sasaki

    CHEMBIOCHEM　16　(8)　1199-1204　2015/05

    DOI： 10.1002/cbic.201500084 　

    ISSN： 1439-4227

    eISSN： 1439-7633

  35. Phosphorylated 5-ethynyl-2 '-deoxyuridine for advanced DNA labeling Peer-reviewed

    Siyoong Seo, Kazumitsu Onizuka, Chieko Nishioka, Eiki Takahashi, Satoshi Tsuneda, Hiroshi Abe, Yoshihiro Ito

    ORGANIC & BIOMOLECULAR CHEMISTRY　13　(15)　4589-4595　2015

    DOI： 10.1039/c5ob00199d 　

    ISSN： 1477-0520

    eISSN： 1477-0539

  36. A new strategy for site-specific alkylation of DNA using oligonucleotides containing an abasic site and alkylating probes Peer-reviewed

    Norihiro Sato, Genichiro Tsuji, Yoshihiro Sasaki, Akira Usami, Takuma Moki, Kazumitsu Onizuka, Ken Yamada, Fumi Nagatsugi

    CHEMICAL COMMUNICATIONS　51　(80)　14885-14888　2015

    DOI： 10.1039/c5cc03915k 　

    ISSN： 1359-7345

    eISSN： 1364-548X

  37. Automatic Pseudorotaxane Formation Targeting on Nucleic Acids Using a Pair of Reactive Oligodeoxynucleotides Peer-reviewed

    Kazumitsu Onizuka, Fumi Nagatsugi, Yoshihiro Ito, Hiroshi Abe

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY　136　(20)　7201-7204　2014/05

    DOI： 10.1021/ja5018283 　

    ISSN： 0002-7863

  38. Remarkable acceleration of a DNA/RNA inter-strand functionality transfer reaction to modify a cytosine residue: the proximity effect via complexation with a metal cation Peer-reviewed

    Daichi Jitsuzaki, Kazumitsu Onizuka, Atsushi Nishimoto, Ikuya Oshiro, Yosuke Taniguchi, Shigeki Sasaki

    NUCLEIC ACIDS RESEARCH　42　(13)　8808-8815　2014

    DOI： 10.1093/nar/gku538 　

    ISSN： 0305-1048

    eISSN： 1362-4962

  39. Short Interfering RNA Guide Strand Modifiers from Computational Screening Peer-reviewed

    Kazumitsu Onizuka, Jason G. Harrison, Alexi A. Ball-Jones, Jose M. Ibarra-Soza, Yuxuan Zheng, Diana Ly, Walter Lam, Stephanie Mac, Dean J. Tantillo, Peter A. Beal

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY　135　(45)　17069-17077　2013/11

    DOI： 10.1021/ja4079754 　

    ISSN： 0002-7863

  40. 4-vinyl-substituted pyrimidine nucleosides exhibit the efficient and selective formation of interstrand cross-links with RNA and duplex DNA Peer-reviewed

    Atsushi Nishimoto, Daichi Jitsuzaki, Kazumitsu Onizuka, Yosuke Taniguchi, Fumi Nagatsugi, Shigeki Sasaki

    NUCLEIC ACIDS RESEARCH　41　(13)　6774-6781　2013/07

    DOI： 10.1093/nar/gkt197 　

    ISSN： 0305-1048

    eISSN： 1362-4962

  41. NEIL1 Binding to DNA Containing 2 '-Fluorothymidine Glycol Stereoisomers and the Effect of Editing Peer-reviewed

    Kazumitsu Onizuka, Jongchan Yeo, Sheila S. David, Peter A. Beal

    CHEMBIOCHEM　13　(9)　1338-1348　2012/06

    DOI： 10.1002/cbic.201200139 　

    ISSN： 1439-4227

  42. Oligodeoxynucleotide containing s-functionalized 2'-deoxy-6-thioguanosine: Facile tools for base-selective and site-specific internal modification of RNA Peer-reviewed

    Shigeki Sasaki, Kazumitsu Onizuka, Yosuke Taniguchi

    Current Protocols in Nucleic Acid Chemistry　1　(48)　4.49.16　2012

    Publisher: Blackwell Publishing Inc.

    DOI： 10.1002/0471142700.nc0449s48 　

    ISSN： 1934-9289 1934-9270

  43. An efficient and simple method for site-selective modification of O-6-methyl-2 '-deoxyguanosine in DNA Peer-reviewed

    Kazumitsu Onizuka, Takamasa Nishioka, Zhichun Li, Daichi Jitsuzaki, Yosuke Taniguchi, Shigeki Sasaki

    CHEMICAL COMMUNICATIONS　48　(33)　3969-3971　2012

    DOI： 10.1039/c2cc17621a 　

    ISSN： 1359-7345

    eISSN： 1364-548X

  44. A NEW TOOL FOR SITE-SPECIFIC CHEMICAL MODIFICATION OF RNA Peer-reviewed

    Shigeki Sasaki, Atsushi Shibata, Natsuki Inaba, Kazumitsu Onizuka, Yosuke Taniguchi

    NUCLEIC ACID THERAPEUTICS　21　(5)　A24-A25　2011/10

    ISSN： 2159-3337

  45. Pin-point chemical modification of RNA with diverse molecules through the functionality transfer reaction and the copper-catalyzed azide-alkyne cycloaddition reaction Peer-reviewed

    Kazumitsu Onizuka, Atsushi Shibata, Yosuke Taniguchi, Shigeki Sasaki

    CHEMICAL COMMUNICATIONS　47　(17)　5004-5006　2011

    DOI： 10.1039/c1cc10582e 　

    ISSN： 1359-7345

    eISSN： 1364-548X

  46. The oligodeoxynucleotide probes for the site-specific modification of RNA Peer-reviewed

    Shigeki Sasaki, Kazumitsu Onizuka, Yosuke Taniguchi

    CHEMICAL SOCIETY REVIEWS　40　(12)　5698-5706　2011

    DOI： 10.1039/c1cs15066a 　

    ISSN： 0306-0012

  47. Activation and Alteration of Base Selectivity by Metal Cations in the Functionality-Transfer Reaction for RNA Modification Peer-reviewed

    Kazumitsu Onizuka, Yosuke Taniguchi, Shigeki Sasaki

    BIOCONJUGATE CHEMISTRY　21　(8)　1508-1512　2010/08

    DOI： 10.1021/bc100131j 　

    ISSN： 1043-1802

  48. A new usage of functionalized oligodeoxynucleotide probe for site-specific modification of a guanine base within RNA Peer-reviewed

    Kazumitsu Onizuka, Yosuke Taniguchi, Shigeki Sasaki

    NUCLEIC ACIDS RESEARCH　38　(5)　1760-1766　2010/03

    DOI： 10.1093/nar/gkp930 　

    ISSN： 0305-1048

    eISSN： 1362-4962

  49. Site-Specific Covalent Modification of RNA Guided by Functionality-Transfer Oligodeoxynucleotides Peer-reviewed

    Kazumitsu Onizuka, Yosuke Taniguchi, Shigeki Sasaki

    BIOCONJUGATE CHEMISTRY　20　(4)　799-803　2009/04

    DOI： 10.1021/bc900009p 　

    ISSN： 1043-1802

  50. Site-specific modification of RNA by functionality-transfer ODN probes.

    Onizuka, K., Taniguchi, Y., Nishioka, T., Sasaki, S.

    Nucleic acids symposium series (2004)　(53)　2009

  51. A NEW ODORLESS PROCEDURE FOR THE SYNTHESIS OF 2 '-DEOXY-6-THIOGUANOSINE AND ITS INCORPORATION INTO OLIGODEOXYNUCLEOTIDES Peer-reviewed

    Kazumitsu Onizuka, Yosuke Taniguchi, Shigeki Sasaki

    NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS　28　(8)　752-760　2009

    DOI： 10.1080/15257770903155576 　

    ISSN： 1525-7770

    eISSN： 1532-2335

  52. Stereoselective synthesis of (+)-2-deoxyolivin based on cycloaddition reaction between the homophthalic anhydride and the chiral cyclohexenone derivative Peer-reviewed

    Yoshinari Haruta, Kazumitsu Onizuka, Kyouichi Watanabe, Kyoko Kono, Akihiro Nohara, Kenichi Kubota, Shuhei Imoto, Shigeki Sasaki

    TETRAHEDRON　64　(30-31)　7211-7218　2008/07

    DOI： 10.1016/j.tet.2008.05.080 　

    ISSN： 0040-4020

  53. Site-specific modification by functionality-transfer oligonucleotide with the photo-inducible reactivity.

    Onizuka, K., Taniguchi, Y., Nishioka, T., Sasaki, S.

    Nucleic acids symposium series (2004)　(52)　2008

  54. Design of S-vinylated 6-thioguanosine as a specific modifier of cytidine Peer-reviewed

    Kazumitsu Onizuka, Yosuke Taniguchi, Shigeki Sasaki

    CHEMISTRY OF NUCLEIC ACID COMPONENTS　10　159-163　2008

  55. Development of novel thioguanosine analogs with the ability to specifically modify cytidine.

    Onizuka, K., Taniguchi, Y., Sasaki, S.

    Nucleic acids symposium series (2004)　(51)　2007

Show all ︎Show first 5

Misc. 3

  1. 核酸反応場を利用した特異な化学反応の開発 ～速く、選択的に、かつユニークに～ Invited

    鬼塚 和光

    生命化学研究レター　(63)　4-9　2021/11

  2. DNAの狙った構造だけを化学修飾する！ー標的と結合した時だけ活性化する新しいアルキル化剤

    永次 史, 鬼塚和光

    化学　75　(2)　52-56　2020/02

  3. 核酸の高次構造を選択的に化学修飾する新規プローブの開発

    永次 史, 鬼塚和光

    生命機能に迫る分子化学　30　86-94　2018/06

Books and Other Publications 2

  1. 進化を続ける核酸化学 : ゲノム編集、非二重らせん、核酸医薬

    永次 史, 鬼塚 和光

    化学同人　2021/10

  2. Middle Molecular Strategy

    Fumi Nagatsugi, Kazumitsu Onizuka

    2021/07

Presentations 84

  1. Chemical and photo-induced crosslinking of a 2ʹ-deoxythioguanosine-functionalized oligo DNA duplex

    Jamila A. Osman, Kazumitsu Onizuka, Yuuhei Yamano, Fumi Nagatsugi

    The 29th French-Japanese Symposium on Medicinal & Fine Chemistry　2025/05/19

  2. Interstrand crosslinking of 2ʹ-deoxythioguanosine-functionalized oligo DNA duplex

    Jamila A. Osman, Kazumitsu Onizuka, Yuuhei Yamano, Fumi Nagatsugi

    The 36th Banyu Sendai Symposium　2025/05/10

  3. 核酸を光化学修飾するための光触媒導入型オリゴDNAプローブの開発

    山野雄平, 鬼塚和光, 佐藤伸一, 永次史

    日本化学会 第105春季年会　2025/03/26

  4. アルキル化分子を用いた細胞内RNA高次構造解析のための技術開発

    畑山妃那, 鬼塚和光, Ping-Yun Lan, Yutong Chen, 宮下映見, 小松リチャード馨, 齊藤博英, 永次史

    日本化学会 第105春季年会　2025/03/26

  5. Interstrand crosslinking of oligonucleotides functionalized with 2ʹ-deoxythioguanosine

    Jamila Abbas Osman, Kazumitsu Onizuka, Yuuhei Yamano, Fumi Nagatsugi

    The 105th CSJ Annual Meeting　2025/03/26

  6. 新規RNA結合性分子プローブの開発とRNA結合性低分子の探索

    長澤瞭佑, 鬼塚和光, 岩田遼平, 都築航祐, 小松リチャード馨, 宮下映見, 壇辻さやか, 村瀬裕貴, 齊藤博英, 次史

    日本化学会 第105春季年会　2025/03/28

  7. Development of pH-dependent RNA-binding molecules with light-up property

    Dylan Christian Thomas, Kazumitsu Onizuka, Ryosuke Nagasawa, Kosuke Tsuzuki, Fumi Nagatsugi

    The 105th CSJ Annual Meeting　2025/03/26

  8. 核酸との相互作用を大規模に解析する化学技術の開発 Invited

    鬼塚 和光

    第10回医薬品開発研究センターシンポジウム　2024/11/14

  9. Synthesis of interstrand crosslinked nucleic acids using 2’- deoxythioguanosine-functionalized oligonucleotides

    Jamila A. Osman, Kazumitsu Onizuka, Yuuhei Yamano, Fumi Nagatsugi

    Young researcher’s symposium of IRT2024　2024/09/07

  10. Analysis of abasic site generation in DNA by photo-catalytic reaction

    Yuuhei Yamano, Kazumitsu Onizuka, Altan Okan, Madoka Sasaki, Ahmed Mostafa, Abdelhady, Fumi Nagatsugi

    IRT2024TOKYO　2024/09/04

  11. Large-scale analysis of RNA alkylations using multiplexed RNA structure libraries

    Kazumitsu Onizuka, Yutong Chen, Emi Miyashita, Kaoru R. Komatsu, Ping-Yun Lan, Hirohide Saito, Fumi Nagatsugi

    IRT2024TOKYO　2024/09/04

  12. Exploration of small molecule-RNA pairs that bind through complementary hydrogen bonds

    Kosuke Tsuzuki, Kazumitsu Onizuka, Ryosuke Nagasawa, Emi Miyashita, Kaoru R. Komatsu, Hirohide Saito, Fumi Nagatsugi

    IRT2024TOKYO　2024/09/04

  13. Synthesis of interstrand crosslinked nucleic acids using 2’- deoxythioguanosine-functionalized oligonucleotides

    Jamila A. Osman, Kazumitsu Onizuka, Yuuhei Yamano, Fumi Nagatsugi

    IRT2024TOKYO　2024/09/03

  14. Formation of pseudorotaxane and catenane by chemically cyclized oligo DNAs

    Kazuki Kuwahara, Kazumitsu Onizuka, Sayaka Yajima, Yuuhei Yamano, Fumi Nagatsugi

    IRT2024TOKYO　2024/09/03

  15. Large-scale analysis of RNA-binding selectivity of a small molecule utilizing structured RNA libraries

    Ryosuke Nagasawa, Kazumitsu Onizuka, Kaoru R. Komatsu, Emi Miyashita, Hirotaka Murase, Mamiko Ozawa, Hirohide Saito, Fumi Nagatsugi

    IRT2024TOKYO　2024/09/03

  16. RNA標的創薬研究に資する 核酸化学ツール開発 Invited

    鬼塚 和光

    第12回 Chem-Bio Joint Seminar 2024　2024/08/27

  17. 水素結合を介して結合するRNA-小分子間ペアの探索

    Kosuke Tsuzuki, Kazumitsu Onizuka, Ryosuke Nagasawa, Emi Miyashita, Kaoru. R. Komatsu, Hirohide Saito, Fumi Nagatsugi

    第12回 Chem-Bio Joint Seminar 2024　2024/08/26

  18. 光触媒反応によるDNA損傷の解析

    山野 雄平, 鬼塚 和光, アルタン オーカン, 佐々木 まどか, アーメド アブデルハーディ, 永次 史

    第12回 Chem-Bio Joint Seminar 2024　2024/08/26

  19. Non-enzymatic abasic site generation in DNA by photo-catalytic reaction

    Yuuhei Yamano, Kazumitsu Onizuka, Altan Okan, Madoka Sasaki, Ahmed Mostafa Abdelhady, Fumi Nagatsugi

    ISBC2024　2024/04/24

  20. Interstrand crosslinking mediated by 2’-deoxythioguanosine-containg oligonucleotides

    Jamila Abbas Osman, Kazumitsu Onizuka, Yuuhei Yamano, Ahmed Mostafa Abdelhady, Fumi Nagatsugi

    ISBC2024　2024/04/24

  21. Elucidation of RNA-binding selectivity of an aminoglycoside-thiazole orange probe by large-scale analysis and its application to RNA binder screening

    Ryosuke Nagasawa, Kazumitsu Onizuka, Kaoru R. Komatsu, Emi Miyashita, Ryohei Iwata, Hirohide Saito, Fumi Nagatsugi

    2024/04/24

  22. Large-scale analysis of small molecule-RNA interactions by barcode microarray method

    Kazumitsu Onizuka, Ryosuke Nagasawa, Ryohei Iwata, Kaoru R. Komatsu, Emi Miyashita, Sayaka Dantsuji, Hirotaka Murase, Mamiko Ozawa, Hirohide Saito, Fumi Nagatsugi

    ISBC2024　2024/04/24

  23. Large-scale analysis of small molecule-RNA interactions and RNA alkylation reactions Invited

    Kazumitsu Onizuka

    The 144th Annual Meeting of the Pharmaceutical Society of Japan Asia Symposium on Pharmaceutical Sciences for the Next Generation: Chemical Biology　2024/03/29

  24. RNA標的創薬に資する RNA-分子間相互作用大規模解析技術開発 Invited

    鬼塚 和光

    日本薬学会第144年会 中分子創薬研究のフロンティア　2024/03/29

  25. Investigation of pull-down unit position for large-scale analysis of RNA alkylation

    Ping-Yun Lan, Kazumitsu Onizuka, Yutong Chen, Emi Miyashita, Kaoru R. Komatsu, Hirohide Saito, Fumi Nagatsugi

    日本化学会 第104春季年会(2024)　2024/03/18

  26. Development of a new screening system to discover RNA-binding small molecules for RNA-targeting therapeutics

    Ryosuke Nagasawa, Kazumitsu Onizuka, Ryohei Iwata, Kaoru R. Komatsu, Emi Miyashita, Sayaka Dantsuji, Hirotaka Murase, Mamiko Ozawa, Hirohide Saito, Fumi Nagatsugi

    2024/03/21

  27. 光酸化によるDNA中のAbasic site生成反応の解析

    Yuuhei Yamano, Kazumitsu Onizuka, Altan Okan, Madoka Sasaki, Ahmed Abdelhady, Fumi Nagatsugi

    2024/03/18

  28. Pseudorotaxane formation by cyclized oligo DNAs and approach to accelerating its formation

    Kazuki Kuwahara, Kazumitsu Onizuka, Sayaka Yajima, Yuuhei Yamano, Fumi Nagatsugi

    2024/03/19

  29. Interstrand crosslinks using oligonucleotides containing 2’-deoxythioguanosine

    Jamila Abbas Osman, Kazumitsu Onizuka, Yuuhei Yamano, Ahmed Mostafa Abdelhady, Fumi Nagatsugi

    日本化学会 第104春季年会(2024)　2024/03/20

  30. Vinyl-quinazolinone (VQ) reagents enable RNA motif detection at single-nucleotide resolution by Next Generation Sequencing (NGS)

    Yutong Chen, Kazumitsu Onizuka, Kaoru R. Komatsu, Emi Miyashita, Hirohide Saito, Fumi Nagatsugi

    日本化学会 第104春季年会(2024)　2024/03/21

  31. Analysis of photo-catalytic abasic site generation in DNA

    Yuuhei Yamano, Kazumitsu Onizuka, Altan Okan, Madoka Sasaki, Ahmed Mostafa Abdelhady, Fumi Nagatsugi

    S-FISNA　2024/02/29

  32. Large-scale analysis of RNA binding of small molecule G-clamp and its applications

    Kazumitsu Onizuka, Ryosuke Nagasawa, Ryohei Iwata, Kaoru R. Komatsu, Emi Miyashita, Sayaka Dantsuji, Hirotaka Murase, Mamiko Ozawa, Hirohide Saito, Fumi Nagatsugi

    S-FISNA　2024/02/29

  33. Creation of base flipping-out structures on DNA and RNA using carbazole-modified thymidine analogs

    Kazumitsu Onizuka, Sayaka Yajima, Yuuhei Yamano, Madoka Sasaki, Ahmed Mostafa Abdelhady, Kei Ishida, Fumi Nagatsugi

    ISNAC2023　2023/11/02

  34. Abasic site generation by photo-catalytic reaction

    Yuuhei Yamano, Kazumitsu Onizuka, Altan Okan, Madoka Sasaki, Ahmed Mostafa Abdelhady, Fumi Nagatsugi

    ISNAC2023　2023/11/01

  35. Interstrand-crosslinking using 2’-deoxythioguanosine-containing oligonucleotides

    Jamila Osman, Kazumitsu Onizuka, Yuuhei Yamano, Ahmed Mostafa Abdelhady, Fumi Nagatsugi

    ISNAC2023　2023/11/02

  36. Development of pyrimidine structure-based alkylating agents for nucleic acids modification

    Ping-Yun Lan, Kazumitsu Onizuka, Yutong Chen, Fumi Nagatsugi

    ISNAC2023　2023/11/01

  37. High-throughput-based approach to comprehensively interrogate proximity-induced RNA alkylation

    Yutong Chen, Kazumitsu Onizuka, Kaoru R. Komatsu, Emi Miyashita, Hirohide Saito, Fumi Nagatsugi

    ISNAC2023　2023/11/01

  38. Large-scale analysis of nucleic acid-protein interactions by using photocatalyst-modified nucleic acid

    Ahmed Mostafa Abdelhady, Kazumitsu Onizuka, Tatsuki Masuzawa, Shinichi Sato, Keita Nakane, Takanori Oyoshi, Fumi Nagatsugi

    ISNAC2023　2023/11/02

  39. Formation of pseudorotaxane and catenane structures using novel cyclized oligodeoxynucleotides

    Kazuki Kuwahara, Kazumitsu Onizuka, Sayaka Yajima, Yuuhei Yamano, Fumi Nagatsugi

    2023/11/01

  40. Development of novel fluorescent indicators to discover new RNA-binding small molecules in FID assay based on large-scale profiles of RNA-indicator interactions

    Ryosuke Nagasawa, Kazumitsu Onizuka, Ryohei Iwata, Kaoru R. Komatsu, Emi Miyashita, Sayaka Dantsuji, Hirotaka Murase, Mamiko Ozawa, Hirohide Saito, Fumi Nagatsugi

    ISNAC2023　2023/11/01

  41. Development of novel fluorescent indicators to discover new RNA-targeting small molecules in FID assay driven by large-scale profiles of RNA-indicator interactions

    Ryosuke Nagasawa, Kazumitsu Onizuka, Ryohei Iwata, Kaoru R. Komatsu, Emi Miyashita, Sayaka Dantsuji, Hirotaka Murase, Mamiko Ozawa, Hirohide Saito, Fumi Nagatsugi

    2023/10/24

  42. Development of nucleic acids alkylating agents based on pyrimidine structure

    Pingyun Lan, Kazumitsu Onizuka, Yutong Chen, Fumi Nagatsugi

    2023/09/08

  43. Development of large-scale analytical approaches for proximity-induced RNA alkylation

    Yutong Chen, Kazumitsu Onizuka, Kaoru R. Komatsu, Emi Miyashita, Hirohide Saito, Fumi Nagatsugi

    2023/09/08

  44. Synthesis of interstrand-crosslinked nucleic acids using 2'-deoxythioguanosine-containing oligonucleotides

    Jamila Osman, Kazumitsu Onizuka, Ahmed Mostafa Abdelhady, Yuuhei Yamano, Fumi Nagatsugi

    2023/09/08

  45. RNA結合性大規模情報を持つ新規蛍光指示薬の開発とRNA結合性小分子のスクリーニング

    長澤 瞭佑, 鬼塚 和光, 岩田 遼平, 小松 馨, 宮下 映見, 壇辻 さやか, 村瀬 裕貴, 小澤 眞美子, 齊藤 博英, 永次 史

    第17回バイオ関連化学シンポジウム　2023/09/08

  46. Large-scale analysis of RNA alkylation reaction with vinyl-quinazolinone (VQ) derivatives

    Yutong Chen, Kazumitsu Onizuka, Kaoru R. Komatsu, Emi Miyashita, Hirohide Saito, Fumi Nagatsugi

    2023/07/05

  47. Development of novel binding-type fluorescent indicators with large-scale data of RNA-binding selectivity

    Ryosuke Nagasawa, Kazumitsu Onizuka, Ryohei Iwata, Kaoru R. Komatsu, Emi Miyashita, Sayaka Dantsuji, Hirotaka Murase, Mamiko Ozawa, Hirohide Saito, Fumi Nagatsugi

    2023/07/05

  48. 新規環状化核酸による擬ロタキサン形成メカニズムの解明とカテナン形成への展開

    桑原和貴, 鬼塚和光, 矢島さやか, 山野雄平, 永次史

    第20回 ホスト-ゲスト・超分子化学シンポジウム　2023/06/17

  49. 擬ロタキサンの貫通方向制御能とカテナン形成能を有する新規環状化核酸の開発

    桑原和貴, 鬼塚和光, 矢島さやか, 山野雄平, 永次史

    日本ケミカルバイオロジー学会 第17回年会　2023/05/29

  50. RNA結合性大規模情報を保持した新規蛍光指示薬の開発と評価

    長澤瞭佑, 鬼塚和光, 岩田遼平, 小松リチャード馨, 宮下映見, 村瀬裕貴, 小澤眞美子, 齊藤博英, 永次史

    日本ケミカルバイオロジー学会 第17回年会　2023/05/29

  51. RNA結合性情報を持つ新規蛍光指示薬の開発

    長澤瞭佑, 鬼塚和光, 岩田 遼平, 小松リチャード馨, 宮下映見, 小澤眞美子, 齊藤博英, 永次史

    日本薬学会第143年会　2023/03/26

  52. Photocatalytic profiling of G4 DNA-interacting proteins

    Ahmed Mostafa Abdelhady, Kazumitsu Onizuka, Shinichi Sato, Tatsuki Masuzawa, Takanori Oyoshi, Fumi Nagatsugi

    2023/03/23

  53. 擬ロタキサンおよびカテナン形成能を持つ新規環状化核酸の開発

    桑原和貴, 鬼塚和光, 矢島さやか, 山野雄平, 永次史

    日本化学会 第103春季年会　2023/03/22

  54. 光触媒導入DNAプローブを利用した核酸光修飾法の開発

    山野雄平, 鬼塚和光, 佐々木まどか, 佐藤伸一, 永次史

    日本化学会 第103春季年会　2023/03/22

  55. Development of reactive OFF-ON type alkylating agents based on pyrimidine structure

    Pingyun Lan, Kazumitsu Onizuka, Yutong Chen, Fumi Nagatsugi

    2023/03/22

  56. Large-scale analysis of RNA alkylation using OFF-ON type alkylators

    Yutong Chen, Kazumitsu Onizuka, Kaoru R. Komatsu, Emi Miyashita, Hirohide Saito, Fumi Nagatsugi

    2023/03/22

  57. RNA結合性および化学反応性の大規模解析

    鬼塚 和光

    JST創発自発的な融合の場 第1回分子生命反応創発討論会　2023/02/21

  58. RNA 標的創薬を指向した結合性小分子スクリーニングシステムの開発

    長澤瞭佑, 鬼塚和光, 小松リチャード馨, 宮下映見, 小澤眞美子, 齊藤博英, 永次史

    理学・生命科学2研究科合同オンラインシンポジウム2023　2023/02/17

  59. Pseudorotaxane and catenane formation via the slipping process

    Kazumitsu Onizuka, Kazuki Kuwahara, Sayaka Yajima, Yuuhei Yamano, Fumi Nagatsugi

    ISNAC2022　2022/11/02

  60. Large-scale analysis of RNA-fluorescence indicator interactions and screening for RNA-binding small molecules

    Ryosuke Nagasawa, Kazumitsu Onizuka, Kaoru R. Komatsu, Emi Miyashita, Mamiko Ozawa, Hirohide Saito, Fumi Nagatsugi

    2022/11/02

  61. Nucleic acids modification by photo-catalytic reaction

    Yuuhei Yamano, Kazumitsu Onizuka, Madoka Sasaki, Shinichi Sato, Fumi Nagatsugi

    ISNAC2022　2022/11/02

  62. Selective photo-catalytic proximity labeling of G4 DNAinteracting proteins for the interaction proteomes of G4 DNA

    Ahmed Mostafa Abdelhady, Kazumitsu Onizuka, Tatsuki Masuzawa, Shinichi Sato, Keita Nakane, Takanori Oyoshi, Fumi Nagatsugi

    ISNAC2022　2022/11/02

  63. Development of a screening system for RNA-binding small molecules based on large-scale information of interactions between RNAs and a fluorescence indicator

    2022/10/25

  64. スリッピング方向が制御可能な貫通構造形成核酸の開発とそのメカニズム解明

    桑原和貴, 鬼塚和光, 矢島さやか, 山野雄平, 永次史

    第12回 CSJ化学フェスタ2022　2022/10/19

  65. Creation of novel fluorescent indicators for screening of RNA binding small molecules

    Ryohei Iwata, Kazumitsu Onizuka, Ryosuke Nagasawa, Hirotaka Murase, Fumi Nagatsugi

    2022/09/18

  66. Development of novel threaded structure-forming nucleic acids with the ability of slipping direction control and their mechanism elucidation

    Kazuki Kuwahara, Kazumitsu Onizuka, Sayaka Yajima, Yuuhei Yamano, Fumi Nagatsugi

    2022/09/17

  67. 光触媒修飾DNAプローブを利用した核酸の光修飾法の開発

    山野雄平, 鬼塚和光, 佐々木まどか, 佐藤伸一, 永次史

    第16回バイオ関連化学シンポジウム　2022/09/12

  68. RNA－蛍光指示薬間相互作用大規模解析とRNA結合分子探索

    鬼塚和光, 長澤瞭佑, 小松リチャード馨, 宮下映見, 岩田遼平, 小澤眞美子, 齊藤博英, 永次史

    第16回バイオ関連化学シンポジウム　2022/09/11

  69. Selective photo-catalytic proximity labeling of G4 DNA-interacting proteins

    2022/08/19

  70. 化学修飾機能性オリゴ核酸の開発研究 Invited

    鬼塚和光

    日本核酸医薬学会 第７回年会　2022/08/01

  71. Selective light-based proximity labeling of DNA-interacting proteins

    Ahmed Mostafa Abdelhady, Kazumitsu Onizuka, Tatsuki Masuzawa, Shinichi Sato, Keita Nakane, Takanori Oyoshi, Fumi Nagatsugi

    2022/07/31

  72. RNA標的創薬を指向したRNA-小分子間化学シグナル大規模解析技術の展開

    鬼塚和光

    新学術領域研究（研究領域提案型）「化学コミュニケーションのフロンティア」第10回公開シンポジウム　2022/07/09

  73. RNA－蛍光指示薬間相互作用大規模情報を利用したRNA結合分子スクリーニング

    長澤瞭佑, 鬼塚和光, 小松リチャード馨, 宮下映見, 小澤眞美子, 齊藤博英, 永次史

    日本ケミカルバイオロジー学会 第16回年会　2022/05/30

  74. RNA-蛍光指示薬間相互作用大規模解析情報を用いた疾患関連pre-miRNA結合分子の探索

    長澤瞭佑, 鬼塚和光, 小松リチャード馨, 宮下映見, 小澤眞美子, 齊藤博英, 永次史

    日本薬学会第142年会　2022/03/28

  75. Selective photo-labeling of G4 DNA-binding protein

    Ahmed Mostafa Abdelhady, Kazumitsu Onizuka, Shinichi Sato, Tatsuki Masuzawa, Takanori Oyoshi, Fumi Nagatsugi

    2022/03/25

  76. RNA結合大規模情報に基づいた新規蛍光指示薬の創製

    岩田 遼平, 鬼塚 和光, 長澤 瞭佑, 村瀬 裕貴, 永次 史

    日本化学会 第102春季年会　2022/03/23

  77. Development of novel OFF-ON type alkylating reagents

    Yutong Chen, Kazumitsu Onizuka, Pingyun Lan, Fumi Nagatsugi

    2022/03/23

  78. Chemical reactions for nucleic acids research Invited

    Kazumitsu Onizuka

    Current Topics in Emergent Materials and Devices-Cooperated with Advanced Research Network in Materials and Devices in Japan 5-Star Alliance, CEFMS-NYCU　2021/10/25

  79. 有機化学的視点からユニークな核酸化学ツールの創製を目指して Invited

    鬼塚 和光

    第3回ABC-InFO講演会 「生体適合化学の進歩」インタラクティブフォーラム　2021/04/23

  80. RNA標的創薬を指向した核酸化学ツール開発 Invited

    鬼塚 和光

    令和5年度日本薬学会東北支部主催 第21回化学系若手研究者セミナー　2023/09/02

  81. RNA標的創薬に資する核酸化学ツール開発

    鬼塚 和光

    第 2 回分子生命反応創発討論会　2023/08/25

  82. 低分子 G-clamp の RNA 結合性大規模解析とその応用 Invited

    鬼塚 和光, 長澤 瞭佑, 岩田 遼平, 村瀬 裕貴, 小松 リチャード馨, 宮下 映見, 小澤 眞美子, 齊藤 博英, 永次 史

    日本核酸医薬学会 第8回年会 若手シンポジウム　2023/07/11

  83. Large-scale analysis of small molecule-RNA interactions and RNA alkylation Invited

    Kazumitsu Onizuka

    The Uehara International Symposium 2023　2023/06/06

  84. 革新的化学ツールによる RNA 機能の制御と理解

    鬼塚和光

    JST創発的研究支援事業「融合の場」第１回公開シンポジウム　2022/06/02

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Industrial Property Rights 1

  1. 核酸内グアニン塩基結合性蛍光色素

    鬼塚 和光, 長澤 瞭佑, 岩田 遼平, 村瀬 裕貴, 永次 史

    Property Type: Patent

Research Projects 8

  1. 新規核酸貫通構造体の構築とmRNA保護法への展開

    鬼塚 和光

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 挑戦的研究(萌芽)

    Institution: 東北大学

    2021/07/09 - 2024/03/31

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    ロタキサンやカテナンといった環状分子を構成成分とする貫通構造体は、そのユニークな構造や性質のため、超分子化学の分野では分子マシンへの展開など様々な研究が試みられている。ロタキサンをキーワードとした研究は数多く行われている一方で、ロタキサン構造構築の難しさのため、生化学分野への応用に関しては未だ課題が多く、更なるブレイクスルーが必要とされている。 本研究では独自の研究で見出した標的核酸塩基のフリップアウトを誘起する機能性核酸を利用し、新しい核酸貫通構造体（ロタキサン様構造）を構築することおよびその機能探索によりその構造体の生物機能、特に翻訳反応のコントロールを目標とし研究を行った。 ①設計した分子の合成：必要なアミダイト体を合成し、DNA自動合成機にて修飾DNAを合成、脱保護・精製後、活性エステル体を用いた機能化により、設計した機能性核酸の合成に成功した。②機能評価：最初にフリップアウト能を2-アミノプリンを用いた蛍光測定により評価した。その結果、機能性核酸は相補鎖の標的塩基を期待通りフリップアウトしていることが示唆された。次に、貫通構造体形成反応を試みた。しかし、様々な検討を行った結果、当初設計した本法で貫通構造体を形成するのは困難であるという結論に至った。代わりの方法として、以前の研究の知見をもとに、テイル鎖をもつ環状化核酸のスリッピングによる貫通構造体形成の改良を試みた。その結果、従来の合成法を大幅に簡便化することに成功し、さらに環状化核酸のテイルの長さ・配列により貫通する速度・方向性を制御できることを新たに明らかにした。

  2. RNA標的創薬を指向したRNA-小分子間化学シグナル大規模解析技術の展開

    鬼塚 和光

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 新学術領域研究(研究領域提案型)

    Institution: 東北大学

    2020/04/01 - 2022/03/31

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    近年、RNA標的創薬はオリゴ核酸に加え、経口投与可能な小・中分子でも効果を期待できる標的が増え、飛躍的に進展している。しかし、RNAへ選択的に結合する分子構造は限られていることから、新たなRNA結合分子解析法・探索法の開発が望まれている。蛍光指示薬競合置換アッセイ(FIDアッセイ)は、RNA結合性分子を効率的に探索するための代表的な方法である。しかし、蛍光指示薬の結合性情報の不足や構造多様性の欠如により、適用可能なRNAや検出できる化合物に限りがあった。本研究では、①蛍光指示薬とRNA相互作用を大規模に解析し相互作用大規模情報を取得すること、②その情報を用いて標的を選択、③FIDアッセイを行い、RNA結合性低分子を探索すること、④蛍光指示薬の構造多様化を目指し研究を行った。①のRNA結合分子の大規模結合情報データベース作成において、複数のRNA結合分子を化学合成し、我々が確立したプルダウン・マイクロアレイ技術を利用することで、RNAライブラリ（3000構造）に対する結合情報を大規模に解析した。特に、蛍光指示薬として多数の例が報告されている、チアゾールオレンジ（TO）系の化合物においては、その結合情報の妥当性も示すことに成功した。次に得られた大規模情報に基づき、疾患関連pre-miRNAと蛍光指示薬の組み合わせを選択し、実際にFIDアッセイによるpre-miRNA結合性分子のハイスループットスクリーニングを行った。その結果、いくつかのヒット化合物を取得し、さらに用いる蛍光指示薬によってヒット化合物が異なることも見出した。蛍光指示薬の拡張に関する研究も行い、良好な成果が得られた。

  3. Development of novel reactive units that activate on higher-order structures of nucleic acids and their application to highly selective inhibitors

    Onizuka Kazumitsu

    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

    2019/04/01 - 2022/03/31

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    In this research, we aimed to create a reactive unit that selectively reacts with the target nucleic acid, and worked on the development of a novel nucleic acid modification unit with target-induced reactivity. As a result, we succeeded in ① discovering an excellent leaving group for target-induced reactivity, ② developing a G-quadruplex (G4) structure-selective reactant, and ③ developing a chemically modified RNA search system. In particular, in ②, we succeeded in developing a parallel G4 structure-selective reactant, and in ③, we succeeded in ranking the reacting RNA easily and on a large scale (1824 types of sequences).

  4. Development for the functional middle size molecules to the high ordered nucleic acidsstructure

    Nagatsugi Fumi

    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

    2015/06/29 - 2020/03/31

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    DNA and RNA can also adopt great varieties of stable higher-order structure motifs, such as the G-quadruplex (G4s), mismatch and bulge. Many of these secondary structures were found to be closely related to the control of the gene expression. Therefore, the higher-order structure of nucleic acids is one of the candidates for therapeutic targets. Due to the therapeutic potentials, efforts on the development of small molecule binders to specifically target the higher-order structures of nucleic acids have been intensely carried out. With the aim to augment the stabilization effect, selective alkylation using small molecules targeting the higher-order structures of nucleic acids have also been pursued. In this research we developed the new middle-size molecules with the binding group to target nucleic acids and the alkylating moiety, for alkylation to higher-order structures of nucleic acids.

  5. Creation of new function of chemically-modified cyclized nucleic acids

    Onizuka Kazumitsu

    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

    2016/04/01 - 2019/03/31

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    Rotaxane is a molecular architecture consisting of a dumbbell-shaped molecule which is threaded through a molecular ring. To further expand the unique properties of the rotaxane into the chemical biology field, a spontaneous rotaxane formation method with the target would be ideal. For example, a functional nucleic acid, which can spontaneously form the rotaxane-like structure with mRNA, might tightly bind to mRNA and strongly inhibit the translation reaction using the static property of the rotaxane. In this study, we inhibited the translation reaction using a pair of pseudorotaxane-forming oligo DNAs developed by our group. In addition, we found that chemically-modified oligo DNA cleaved the target RNA.

  6. 核酸上を一次元的に動く分子マシンの開発

    鬼塚 和光

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 新学術領域研究(研究領域提案型)

    Institution: 東北大学

    2015/04/01 - 2017/03/31

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    本研究では、標的核酸に対して貫通構造体を自発的に構築し、さらにその分子の動きを制御可能な人工核酸の開発を目指した。前年度までに我々は、２種類の方法、化学反応を利用する方法とスリッピングによる方法で貫通構造体を高効率、高収率で形成することに成功し、70℃以上の高温条件下では環状化した人工核酸を動かすことにも成功していた。 本年度では、前年度までに確立した基礎技術を発展させ、37℃の条件下でも動的挙動が可能な人工核酸の開発に取り組んだ。具体的には、環状化する際にできる環状外部のテイル鎖の根元に光切断可能なo-ニトロベンジル基を修飾したリンカーを挿入した新しい人工核酸pcDNAを合成した。このpcDNAを用いてまず貫通構造体形成を試みたところ、期待通りの収率・効率で形成反応が進行した。続いてその構造体に365 nmの光を5分間照射することで、環状化したpcDNAの二つのテイル鎖を切断した。これにより、期待通り環状化核酸の熱的安定性を著しく低下させることができ、標的核酸から解離させることに成功した。さらに、光照射後、もう一度pcDNAを作用させたところ、再度貫通構造体を形成できたことから、この環状化核酸は光により標的DNA上を動いていることが示された。このような機能を持つ分子は核酸上を一次元的に動く光駆動型の分子マシンということができ、当初の目標を達成することができた。本研究で開発した基盤技術はさらに発展させることで、分子メモリーや分子ロボットの記憶に関するシステムへ展開できると考えている。

  7. Development of a novel method to control translation by pseudorotaxane formation targeting on RNA

    Onizuka Kazumitsu

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Young Scientists (B)

    Institution: Tohoku University

    2014/04/01 - 2016/03/31

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    It is expected that forming rotaxane-like architecture on target mRNA will lead to the regulation of gene expression. In this study, we tried to form pseudorotaxane architecture on the target RNA using a pair of pseudorotaxane-forming oligo DNAs (prfODNs) under physiological conditions. The pseudorotaxane formation reaction proceeded in 85% for 5 min, that is, we have developed the high-performance prfODN with high efficiency and yield.

  8. RNAの選択的化学修飾を目指した官能基転移能を持つ人工核酸の開発

    鬼塚 和光

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 特別研究員奨励費

    Institution: 九州大学

    2008 - 2010

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    本研究ではRNAの部位特異的修飾を目指し、官能基を転移する機能性核酸の開発を行った。これまでに、ジカルボニル型のα,β不飽和ケトンを転移基とすることで、中性条件下でシトシンに対して、アルカリ性条件下または遷移金属カチオン存在下でグアニンに対して選択的な修飾に成功していた。引き続き、金属錯体形成による転移官能基活性化を検討するため、金属キレート部位をもつ2-ピリジンモノケトン型転移基を設計した。様々な2価の金属カチオンを用いて反応の検討を行ったところ、触媒量のNi^<2+>でシトシン選択的に進行することを見出した。さらに大過剰のNi^<2+>存在下では選択性がグアニンに変わることも見出した。2-ピリジンモノケトン型転移基は、金属非存在下では非常に安定であること、極微量の金属によって反応の制御が可能であることから、ラベル化やRNA編集技術等様々な展開が可能である。 次に官能基転移反応をクリック反応と組み合わせることで、簡便かつ効率的なRNAの部位特異的修飾法を検討した。具体的には、末端アルキンを持つ転移基を合成し転移反応の検討を行った。その結果、わずか10分で90%のRNAを修飾することに成功した。続いて、蛍光基やビオチン等の様々な化合物のアジド体を用いクリック反応を行った。反応は単純な化合物では10分以内に、大きな化合物でも50分以内に定量的に進行した。さらにこのラベル化法をmRNAに対して行ったところ、ビオチン基を修飾することに成功した。この迅速かつ高収率なラベル化法は、これまでにない画期的な手法であり、今後、多種多様の修飾が可能になると考えている。

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