Updated on 2022/06/02

写真a

 
KIMURA Yasuaki
 
Organization
Graduate School of Science Associate professor
Graduate School
Graduate School of Science
Undergraduate School
School of Science Department of Chemistry
Title
Associate professor

Degree 1

  1. 博士(薬学) ( 2013.3   東京大学 ) 

Research Interests 5

  1. 創薬化学

  2. ケミカルバイオロジー

  3. RNA

  4. 核酸化学

  5. 核酸医薬

Research Areas 3

  1. Life Science / Pharmaceutical chemistry and drug development sciences

  2. Nanotechnology/Materials / Bio chemistry

  3. Nanotechnology/Materials / Chemical biology

Research History 7

  1. Nagoya University   Graduate School of Science   Lecturer

    2020.7

  2. Nagoya University   Lecturer

    2020.7

  3. Nagoya University   Institute for Advanced Research

    2017.6 - 2020.6

  4. 名古屋大学大学院   理学研究科   助教

    2015.7 - 2020.6

  5. 東京大学大学院   薬学系研究科   特任助教

    2015.4 - 2015.6

  6. ERATO金井触媒分子生命プロジェクト特任研究員   東京大大学院薬学系研究科

    2013.4 - 2015.6

  7. 日本学術振興会特別研究員(DC1)

    2010.4 - 2013.3

▼display all

Education 1

  1. 東京大学大学院   薬学系研究科   分子薬学専攻

    2008.4 - 2013.3

Professional Memberships 4

  1. THE CHEMICAL SOCIETY OF JAPAN

  2. JAPANESE SOCIETY FOR CHEMICAL BIOLOGY

  3. The Japan Society of Nucleic Acids Chemistry

  4. NUCLEIC ACIDS THERAPEUTICS SOCIETY OF JAPAN

Awards 2

  1. 日本核酸化学会 大塚賞

    2018.11  

    木村康明

  2. 大津会議アワードフェロー

    2011.10   公益財団法人MSD生命科学財団  

    木村康明

 

Papers 37

  1. Complete Chemical Synthesis of Minimal Messenger RNA by Efficient Chemical Capping Reaction.

    Abe N, Imaeda A, Inagaki M, Li Z, Kawaguchi D, Onda K, Nakashima Y, Uchida S, Hashiya F, Kimura Y, Abe H

    ACS chemical biology     2022.5

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    DOI: 10.1021/acschembio.1c00996

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  2. Development of Fluorophosphoramidate as a Biocompatibly Transformable Functional Group and its Application as a Phosphate Prodrug for Nucleoside Analogs

    Yoshida Yuki, Zheng Ti, Tanabe Wataru, Tomoike Fumiaki, Hashiya Fumitaka, Suzuki Tetsuro, Hirota Shuto, Saiki Yuriko, Horii Akira, Hirayama Akiyoshi, Soga Tomoyosi, Kimura Yasuaki, Abe Hiroshi

    CHEMMEDCHEM     page: e202200188   2022.4

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:ChemMedChem  

    Synthetic phosphate-derived functional groups are important for controlling the function of bioactive molecules in vivo. Herein we describe the development of a new type of biocompatible phosphate analog, a fluorophosphoramidate (FPA) functional group that has characteristic P−F and P−N bonds. We found that FPA with a primary amino group was relatively unstable in aqueous solution and was converted to a monophosphate, while FPA with a secondary amino group was stable. Furthermore, by improving the molecular design of FPA, we developed a reaction in which a secondary amino group is converted to a primary amino group in the intracellular environment and clarified that the FPA group functions as a phosphate prodrug of nucleoside. Various FPA-gemcitabine derivatives were synthesized and their toxicity to cancer cells were evaluated. One of the FPA-gemcitabine derivatives showed superior toxicity compared with gemcitabine and its ProTide prodrug, which methodology is widely used in various nucleoside analogs, including anti-cancer and anti-virus drugs.

    DOI: 10.1002/cmdc.202200188

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  3. SYNTHESIS AND BIOLOGICAL EVALUATION OF NMDI14 DERIVATIVES AS ANTI-MESOTHELIOMA AGENTS International journal

    Hong Nhung Nguyen, Suzuki Koya, Kimura Yasuaki, Hirokawa Takatsugu, Murakami-Tonami Yuko, Abe Hiroshi

    HETEROCYCLES   Vol. 100 ( 2 ) page: 253 - 266   2020.2

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Heterocycles  

    Mesothelioma is a severe tumor formed in pleura and peritoneum, for which no useful molecular-targeting therapy is available. We synthesized several derivatives of NMDI14, which is a reported inhibitor for non-sense mediated mRNA decay, and evaluated the activity of the NMDI14 derivatives as potential anti-mesothelioma agents. Some of the synthesized compounds showed promising activity in terms of cytotoxicity toward mesothelioma model cells and promotion of GAS5 expression selectively in mesothelioma cells. These results indicate that the NMDI14 derivatives may be useful for further developing clinically effective anti-mesothelioma drugs.

    DOI: 10.3987/COM-19-14191

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  4. Intracellular Delivery of Antisense DNA and siRNA with Amino Groups Masked with Disulfide Units International journal

    Shu Zhaoma, Ota Azumi, Takayama Yukiya, Katsurada Yuri, Kusamori Kosuke, Abe Naoko, Nakamoto Kosuke, Tomoike Fumiaki, Tada Seiichi, Ito Yoshihiro, Nishikawa Makiya, Kimura Yasuaki, Abe Hiroshi

    CHEMICAL & PHARMACEUTICAL BULLETIN   Vol. 68 ( 2 ) page: 129 - 132   2020.2

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  5. Intracellular Delivery of Antisense DNA and siRNA with Amino Groups Masked with Disulfide Units International journal

    Shu Zhaoma, Ito Yoshihiro, Nishikawa Makiya, Kimura Yasuaki, Kusamori Kosuke, Abe Naoko, Nakamoto Kosuke, Tomoike Fumiaki, Tada Seiichi

    Chemical and Pharmaceutical Bulletin   Vol. 68 ( 2 ) page: 129 - 132   2020

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:The Pharmaceutical Society of Japan  

    <p>Efficient methods for delivery of antisense DNA or small interfering RNA (siRNA) are highly needed. Cationic materials, which are conventionally used for anionic oligonucleotide delivery, have several drawbacks, including aggregate formation, cytotoxicity and a low endosome escape efficiency. In this report a bio-reactive mask (<i>i.e.</i>, disulfide unit) for cationic amino groups was introduced, and the mask was designed such that it was removed at the target cell surface. Insolubility and severe cellular toxicity caused by exposed cationic groups are avoided when using the mask. Moreover, the disulfide unit used to mask the cationic group enabled direct delivery of oligonucleotides to the cell cytosol. The molecular design reported is a promising approach for therapeutic applications.</p>

    DOI: 10.1248/cpb.c19-00811

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  6. Antisense Oligonucleotide Modified with Disulfide Units Induces Efficient Exon Skipping in mdx Myotubes through Enhanced Membrane Permeability and Nucleus Internalization

    Haruka Hiraoka, Zhaoma Shu, Bao Tri Le, Keiko Masuda, Kosuke Nakamoto, Lyu Fangjie, Naoko Abe, Fumitaka Hashiya, Yasuaki Kimura, Yoshihiro Shimizu, Rakesh N. Veedu, Hiroshi Abe

    ChemBioChem   Vol. 22 ( 24 ) page: 3437 - 3442   2021.12

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    DOI: 10.1002/cbic.202100413

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  7. Completely Chemically Synthesized Long DNA Can be Transcribed in Human Cells

    Kazuki Yamaoka, Ryota Oikawa, Naoko Abe, Kosuke Nakamoto, Fumiaki Tomoike, Fumitaka Hashiya, Yasuaki Kimura, Hiroshi Abe

    ChemBioChem   Vol. 22 ( 23 ) page: 3273 - 3276   2021.12

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    DOI: 10.1002/cbic.202100312

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  8. Structure, Synthesis and Inhibition Mechanism of Nucleoside Analogues as HIV‐1 Reverse Transcriptase Inhibitors (NRTIs) Reviewed International journal

    Yuki Yoshida, Masakazu Honma, Yasuaki Kimura, Hiroshi Abe

    ChemMedChem   Vol. 16 ( 5 ) page: 743 - 766   2021.3

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    DOI: 10.1002/cmdc.202000695

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    Other Link: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/cmdc.202000695

  9. Phosphorothioate Modification of mRNA Accelerates the Rate of Translation Initiation to Provide More Efficient Protein Synthesis Reviewed

    Daisuke Kawaguchi, Ayumi Kodama, Naoko Abe, Kei Takebuchi, Fumitaka Hashiya, Fumiaki Tomoike, Kosuke Nakamoto, Yasuaki Kimura, Yoshihiro Shimizu, Hiroshi Abe

    Angewandte Chemie International Edition   Vol. 59 ( 40 ) page: 17403 - 17407   2020.9

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    DOI: 10.1002/anie.202007111

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    Other Link: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/anie.202007111

  10. Free-Energy Calculation of Ribonucleic Inosines and Its Application to Nearest-Neighbor Parameters. Reviewed International journal

    Shun Sakuraba, Junichi Iwakiri, Michiaki Hamada, Tomoshi Kameda, Genichiro Tsuji, Yasuaki Kimura, Hiroshi Abe, Kiyoshi Asai

    Journal of chemical theory and computation   Vol. 16 ( 9 ) page: 5923 - 5935   2020.9

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    Can current simulations quantitatively predict the stability of ribonucleic acids (RNAs)? In this research, we apply a free-energy perturbation simulation of RNAs containing inosine, a modified ribonucleic base, to the derivation of RNA nearest-neighbor parameters. A parameter set derived solely from 30 simulations was used to predict the free-energy difference of the RNA duplex with a mean unbiased error of 0.70 kcal/mol, which is a level of accuracy comparable to that obtained with parameters derived from 25 experiments. We further show that the error can be lowered to 0.60 kcal/mol by combining the simulation-derived free-energy differences with experimentally measured differences. This protocol can be used as a versatile method for deriving nearest-neighbor parameters of RNAs with various modified bases.

    DOI: 10.1021/acs.jctc.0c00270

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  11. Chemically synthesized circular RNAs with phosphoramidate linkages enable rolling circle translation Reviewed International journal

    Kosuke Nakamoto, Naoko Abe, Genichiro Tsuji, Yasuaki Kimura, Fumiaki Tomoike, Yoshihiro Shimizu, Hiroshi Abe

    Chemical Communications   Vol. 56 ( 46 ) page: 6217 - 6220   2020.6

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Royal Society of Chemistry (RSC)  

    <p>Circular RNA without a stop codon enables rolling circle translation. we carried out one-pot chemical synthesis of circular RNA from RNA fragments. The synthesized circular RNAs acted as translation templates, despite the presence of unnatural phosphoramidate linkages.</p>

    DOI: 10.1039/d0cc02140g

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  12. Translational control by secondary-structure formation in mRNA in a eukaryotic system Reviewed International journal

    Daisuke Kawaguchi, Saaya Shimizu, Naoko Abe, Fumitaka Hashiya, Fumiaki Tomoike, Yasuaki Kimura, Hiroshi Abe

    Nucleosides, Nucleotides & Nucleic Acids   Vol. 39 ( 1-3 ) page: 195 - 203   2020.2

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Informa UK Limited  

    Eukaryotic mRNA has a cap structure at the 5' end and a poly(A) tail at the 3' end. The cap and poly(A) tail form a complex with multiple translation factors, and mRNA forms a circularized structure called a closed-loop model. This circularized structure reportedly not only stabilizes mRNA but also promotes ribosome recycling during translation, which improves translation efficiency. We designed an artificial mRNA that forms a circularized structure without a cap structure and poly(A) tail and found that its translational efficiency was improved compared with that of a sequence without the circularized structure in a eukaryotic translation system.

    DOI: 10.1080/15257770.2019.1671593

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  13. A robust model for quantitative prediction of the silencing efficacy of wild-type and A-to-I edited miRNAs. Reviewed International journal

    Shen Tian, Goro Terai, Yoshiaki Kobayashi, Yasuaki Kimura, Hiroshi Abe, Kiyoshi Asai, Kumiko Ui-Tei

    RNA biology   Vol. 17 ( 2 ) page: 264 - 280   2020.2

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Taylor & Francis  

    MicroRNAs (miRNAs) are small non-coding RNAs that play essential roles in the regulation of gene function by a mechanism known as RNA silencing. In a previous study, we revealed that miRNA-mediated silencing efficacy is correlated with the combinatorial thermodynamic properties of the miRNA seed-target mRNA duplex and the 5´-terminus of the miRNA duplex, which can be predicted using 'miScore'. In this study, a robust refined-miScore was developed by integrating the thermodynamic properties of various miRNA secondary structures and the latest thermodynamic parameters of wobble base-pairing, including newly established parameters for I:C base pairing. Through repeated random sampling and machine learning, refined-miScore models calculated with either melting temperature (Tm) or free energy change (ΔG) values were successfully built and validated in both wild-type and adenosine-to-inosine edited miRNAs. In addition to the previously reported contribution of the seed-target duplex and 5´-terminus region, the refined-miScore suggests that the central and 3´-terminus regions of the miRNA duplex also play a role in the thermodynamic regulation of miRNA-mediated silencing efficacy.

    DOI: 10.1080/15476286.2019.1678364

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  14. Intracellular build-up RNAi with single-strand circular RNAs as siRNA precursors Reviewed International journal

    Yasuaki Kimura, Zhaoma Shu, Mika Ito, Naoko Abe, Kosuke Nakamoto, Fumiaki Tomoike, Satoshi Shuto, Yoshihiro Ito, Hiroshi Abe

    Chemical Communications   Vol. 56 ( 3 ) page: 466 - 469   2020.1

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    Authorship:Lead author   Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Royal Society of Chemistry ({RSC})  

    DOI: 10.1039/c9cc04872c

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  15. SYNTHESIS AND BIOLOGICAL EVALUATION OF NMDI14 DERIVATIVES AS ANTI-MESOTHELIOMA AGENTS Reviewed International journal

    Hong Nhung Nguyen, Suzuki Koya, Kimura Yasuaki, Hirokawa Takatsugu, Murakami-Tonami Yuko, Abe Hiroshi

    Heterocycles   Vol. 100 ( 2 ) page: 253 - 266   2020.1

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  16. N6-methyl adenosine in siRNA evades immune response without reducing RNAi activity Reviewed International journal

    Akihiro Imaeda, Fumiaki Tomoike, Mayu Hayakawa, Kosuke Nakamoto, Yasuaki Kimura, Naoko Abe, Hiroshi Abe

    Nucleosides, Nucleotides and Nucleic Acids   Vol. 38 ( 12 ) page: 972 - 979   2019.12

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Taylor & Francis  

    PMID: 31298608

    DOI: 10.1080/15257770.2019.1641205

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  17. Intracellular delivery of Antisense DNA and siRNA with amino groups masked with disulfide units Reviewed International journal

    Zhaoma Shu, Azumi Ota, Yukiya Takayama, Yuri Katsurada, Kosuke Kusamori, Naoko Abe, Kosuke Nakamoto, Fumiaki Tomoike, Seiichi Tada, Yoshihiro Ito, Makiya Nishikawa, Yasuaki Kimura, Hiroshi Abe

      Vol. 68 ( 2 ) page: 129 - 132   2019.12

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  18. Disulfide-Unit Conjugation Enables Ultrafast Cytosolic Internalization of Antisense DNA and siRNA Reviewed International journal

    Zhaoma Shu, Iku Tanaka, Azumi Ota, Daichi Fushihara, Dr. Naoko Abe, Saki Kawaguchi, Dr. Kosuke, Nakamoto, Dr. Fumiaki Tomoike, Dr. Seiichi Tada, Prof. Yoshihiro Ito, Dr, Yasuaki Kimura, Prof. Hiroshi Abe

    Angew. Chem., Int. Ed.   Vol. 58 ( 20 ) page: 6611 - 6615   2019.5

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/anie.201900993

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  19. Disulfide‐Unit Conjugation Enables Ultrafast Cytosolic Internalization of Antisense DNA and siRNA Reviewed International journal

    Zhaoma Shu, Iku Tanaka, Azumi Ota, Daichi Fushihara, Naoko Abe, Saki Kawaguchi, Kosuke Nakamoto, Fumiaki Tomoike, Seiichi Tada, Yoshihiro Ito, Yasuaki Kimura, Hiroshi Abe

    Angewandte Chemie   Vol. 131 ( 20 ) page: 6683   2019.5

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    DOI: 10.1002/ange.201900993

  20. A Covalent Inhibitor for Glutathione S-Transferase Pi (GSTP1-1 ) in Human Cells. Reviewed International journal

    Yuko Shishido, Fumiaki Tomoike, Keiko Kuwata, Haruka Fujikawa, Yoshitaka Sekido, Yuko Murakami-Tonami, Tomoshi Kameda, Naoko Abe, Yasuaki Kimura, Satoshi Shuto, Hiroshi Abe

    Chembiochem : a European journal of chemical biology   Vol. 20 ( 7 ) page: 900 - 905   2019.4

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    Glutathione S-transferase π (GSTP1-1 ) is overexpressed in many types of cancer and is involved in drug resistance. Therefore, GSTP1-1 is an important target in cancer therapy, and many GST inhibitors have been reported. We had previously developed an irreversible inhibitor, GS-ESF, as an effective GST inhibitor; however, its cellular permeability was too low for it to be used in inhibiting intracellular GST. We have now developed new irreversible inhibitors by introducing sulfonyl fluoride (SF) into chloronitrobenzene (CNB). The mechanism of action was revealed to be that CNBSF first reacts with glutathione (GSH) through an aromatic substitution in the cell, then the sulfonyl group on the GSH conjugate with CNBSF reacts with Tyr108 of GST to form a sulfonyl ester bond. Our new inhibitor irreversible inhibited GSTP1-1 both in vitro and in cellulo with a long duration of action.

    DOI: 10.1002/cbic.201800671

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    Other Link: http://orcid.org/0000-0002-3609-602X

  21. 膜透過性を有するGST共有結合性阻害剤の開発

    友池 史明, 宍戸 裕子, 藤川 遥加, 木村 康明, 桑田 啓子, 村上 優子, 福井 健二, 関戸 好孝, 矢野 貴人, 亀田 倫史, 周東 智, 阿部 洋

    日本薬学会年会要旨集   Vol. 139年会 ( 2 ) page: 80 - 80   2019.3

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:(公社)日本薬学会  

  22. Nearest-neighbor parameter for inosine-cytosine pairs through a combined experimental and computational approach Reviewed International journal

    Shun Sakuraba, Junichi Iwakiri, Michiaki Hamada, Tomoshi Kameda, Genichiro Tsuji, Yasuaki Kimura, Hiroshi Abe, Kiyoshi Asai

        2018.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Cold Spring Harbor Laboratory  

    <title>Abstract</title>In RNA secondary structure prediction, nearest-neighbor parameters are used to determine the stability of a given structure. We derived the nearest-neighbor parameters for RNAs containing inosine-cytosine pairs. For parameter derivation, we developed a method that combines UV adsorption measurement experiments with free-energy calculations using molecular dynamics simulations. The method provides fast drop-in parameters for modified bases. Derived parameters were compared and found to be consistent with existing parameters for canonical RNAs. A duplex with an internal inosine-cytosine pair is 0.9 kcal/mol more unstable than the same duplex with an internal guanine-cytosine pair, and is as stable as the one with an internal adenine-uracil pair (only 0.1 kcal/mol more stable) on average.

    DOI: 10.1101/454124

  23. Chemical ligation reaction for oligonucleotides based on electrophilic phosphorothioester

    Kimura Yasuaki, Maruyama Hideto, Oikawa Ryota, Hayakawa Mayu, Abe Naoko, Tsuji Genichiro, Matsuda Akira, Shuto Satoshi, Ito Yoshihiro, Abe Hiroshi

    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY   Vol. 255   page: .   2018.3

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  24. Nano structure design for RNA interference

    Shu Zhaoma, Abe Naoko, Tomoike Fumiaki, Kimura Yasuaki, Ito Yoshihiro, Abe Hiroshi

    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY   Vol. 255   page: .   2018.3

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  25. Development of glutathione S-transferase (GST) covalent inhibitor

    Shishido Yuko, Tomoike Fumiaki, Kimura Yasuaki, Kuwata Keiko, Yano Takato, Fukui Kenji, Fujikawa Haruka, Sekido Yoshitaka, Murakami-Tonami Yuko, Kameda Tomoshi, Shuto Satoshi, Abe Hiroshi

    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY   Vol. 255   page: .   2018.3

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  26. Chemical ligation reaction for oligonucleotides based on electrophilic phosphorothioester Reviewed International journal

    Kimura Yasuaki, Maruyama Hideto, Oikawa Ryota, Hayakawa Mayu, Abe Naoko, Tsuji Genichiro, Matsuda Akira, Shuto Satoshi, Ito Yoshihiro, Abe Hiroshi

    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY   Vol. 255   2018.3

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  27. Chemical Ligation Reactions of Oligonucleotides for Biological and Medicinal Applications

    Abe Hiroshi, Kimura Yasuaki

    CHEMICAL & PHARMACEUTICAL BULLETIN   Vol. 66 ( 2 ) page: 117-122   2018.2

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  28. Chemical Ligation Reactions of Oligonucleotides for Biological and Medicinal Applications Reviewed International journal

    Hiroshi Abe, Yasuaki Kimura

    Chemical and Pharmaceutical Bulletin   Vol. 66 ( 2 ) page: 117 - 122   2018

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Pharmaceutical Society of Japan  

    Chemical ligation of oligonucleotides (ONs) is the key reaction for various ON-based technologies. We have tried to solve the problems of RNA interference (RNAi) technology by applying ON chemical ligation to RNAi. We designed a new RNAi system, called intracellular buildup RNAi (IBR-RNAi), where the RNA fragments are built up into active small-interference RNA (siRNA) in cells through a chemical ligation reaction. Using the phosphorothioate and iodoacetyl groups as reactive functional groups for the ligation, we achieved RNAi effects without inducing immune responses. Additionally, we developed a new chemical ligation for IBR-RNAi, which affords a more native-like structure in the ligated product. The new ligation method should be useful not only for IBR-RNAi but also for the chemical synthesis of biofunctional ONs.

    DOI: 10.1248/cpb.c17-00615

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  29. グルタチオン-S-トランスフェラーゼを標的とした共有結合性阻害剤の開発

    宍戸 裕子, 藤川 遥加, 友池 史明, 木村 康明, 桑田 啓子, 村上 優子, 福井 健二, 関戸 好孝, 矢野 貴人, 周東 智, 阿部 洋

    生命科学系学会合同年次大会   Vol. 2017年度   page: [3P - 0205]   2017.12

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:生命科学系学会合同年次大会運営事務局  

  30. A covalent G-site inhibitor for glutathione S-transferase Pi (GSTP(1-1)) Reviewed International journal

    Yuko Shishido, Fumiaki Tomoike, Yasuaki Kimura, Keiko Kuwata, Takato Yano, Kenji Fukui, Haruka Fujikawa, Yoshitaka Sekido, Yuko Murakami-Tonami, Tomoshi Kameda, Satoshi Shuto, Hiroshi Abe

    CHEMICAL COMMUNICATIONS   Vol. 53 ( 81 ) page: 11138 - 11141   2017.10

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:ROYAL SOC CHEMISTRY  

    We herein report the first covalent G-site-binding inhibitor for GST, GS-ESF (1), which irreversibly inhibited the GSTP1-1 function. LC-MS/MS and X-ray structure analyses of the covalently linked GST-inhibitor complex suggested that 1 reacted with Tyr108 of GSTP1-1. The mechanism of covalent bond formation was discussed based on MD simulation results.

    DOI: 10.1039/c7cc05829b

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  31. Chemical ligation of oligonucleotides using an electrophilic phosphorothioester Reviewed International journal

    Hideto Maruyama, Ryota Oikawa, Mayu Hayakawa, Shono Takamori, Yasuaki Kimura, Naoko Abe, Genichiro Tsuji, Akira Matsuda, Satoshi Shuto, Yoshihiro Ito, Hiroshi Abe

    NUCLEIC ACIDS RESEARCH   Vol. 45 ( 12 ) page: 7042 - 7048   2017.7

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:OXFORD UNIV PRESS  

    We developed a new approach for chemical ligation of oligonucleotides using the electrophilic phosphorothioester (EPT) group. A nucleophilic phosphorothioate group on oligonucleotides was converted into the EPT group by treatment with Sanger's reagent (1-fluoro-2,4-dinitrobenzene). EPT oligonucleotides can be isolated, stored frozen, and used for the ligation reaction. The reaction of the EPT oligonucleotide and an amino-modified oligonucleotide took place without any extra reagents at pH 7.0-8.0 at room temperature, and resulted in a ligation product with a phosphoramidate bond with a 39-85% yield. Thismethod has potential uses in biotechnology and chemical biology.

    DOI: 10.1093/nar/gkx459

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  32. Supramolecular Ligands for Histone Tails by Employing a Multivalent Display of Trisulfonated Calix[4]arenes Reviewed

    Yasuaki Kimura, Nae Saito, Kayo Hanada, Jiaan Liu, Takayoshi Okabe, Shigehiro A. Kawashima, Kenzo Yamatsugu, Motomu Kanai

    CHEMBIOCHEM   Vol. 16 ( 18 ) page: 2599 - 604   2015.12

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    Publishing type:Research paper (scientific journal)   Publisher:WILEY-V C H VERLAG GMBH  

    Post-translational modification of histone tails plays critical roles in gene regulation. Thus, molecules recognizing histone tails and controlling their epigenetic modification are desirable as biochemical tools to elucidate regulatory mechanisms. There are, however, only a few synthetic ligands that bind to histone tails with substantial affinity. We report CA2 and CA3, which exhibited sub-micromolar affinity to histone tails (especially tails with a trimethylated lysine). Multivalent display of trisulfonated calix[4] arene was important for strong binding. CA2 was applicable not only to synthetic tail peptides but also to endogenous histone proteins, and was successfully used to pull-down endogenous histones from nuclear extract. These findings indicate the utility of these supramolecular ligands as biochemical tools for studying chromatin regulator protein and as a targeting motif in ligand-directed catalysis to control epigenetic modifications.

    DOI: 10.1002/cbic.201500448

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  33. Catalytic Anomeric Aminoalkynylation of Unprotected Aldoses Reviewed

    Yasuaki Kimura, Soichi Ito, Yohei Shimizu, Motomu Kanai

    ORGANIC LETTERS   Vol. 15 ( 16 ) page: 4130 - 3   2013.8

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:AMER CHEMICAL SOC  

    A copper(I)-catalyzed anomeric aminoalkynylation reaction of unprotected aldoses was realized. Use of an electron-deficient phosphine ligand, boric acid to stabilize the iminium intermediate, and a protic additive (IPA) to presumably enhance reversible carbohydrate-boron complexation were all essential for efficient conversion. The reaction proceeded well even with a natural disaccharide substrate, suggesting that the developed catalytic reaction could be useful for the synthesis of glycoconjugates with minimum use of protecting groups.

    DOI: 10.1021/ol401810b

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    PubMed

  34. Inhibition of MAO-A and stimulation of behavioural activities in mice by the inactive prodrug form of the anti-influenza agent oseltamivir Reviewed

    Miki Hiasa, Yumiko Isoda, Yasushi Kishimoto, Kenta Saitoh, Yasuaki Kimura, Motomu Kanai, Masakatsu Shibasaki, Dai Hatakeyama, Yutaka Kirino, Takashi Kuzuhara

    British Journal of Pharmacology   Vol. 169 ( 1 ) page: 115 - 29   2013.5

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    Background and Purpose Oseltamivir is the most widely prescribed anti-influenza medication. However, in rare instances, it has been reported to stimulate behavioural activities in adolescents. The goal of this study was to determine the molecular mechanism responsible for these behavioural activities. Experimental Approach We performed an in vitro assay of MAO-A, the enzyme responsible for neurotransmitter degradation, using either the active form - oseltamivir carboxylate (OC) or the inactive prodrug - oseltamivir ethyl ester (OEE). We also analysed the docking of MAO-A with OEE or OC in silico. Mouse behaviours after OEE or OC administration were monitored using automated video and computer analysis. Key Results OEE, but not OC, competitively and selectively inhibited human MAO-A. The estimated Ki value was comparable with the Km values of native substrates of MAO-A. Docking simulations in silico based on the tertiary structure of MAO-A suggested that OEE could fit into the inner pocket of the enzyme. Behavioural monitoring using automated video analysis further revealed that OEE, not OC, significantly enhanced spontaneous behavioural activities in mice, such as jumping, rearing, sniffing, turning and walking. Conclusions and Implications Our multilevel analyses suggested OEE to be the cause of the side effects associated with oseltamivir and revealed the molecular mechanism underlying the stimulated behaviours induced by oseltamivir in some circumstances. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.

    DOI: 10.1111/bph.12102

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    PubMed

  35. Design and Synthesis of Resin-Conjugated Tamiflu Analogs for Affinity Chromatography Reviewed

    Yasuaki Kimura, Kenzo Yamatsugu, Motomu Kanai, Noriko Echigo, Takashi Kuzuhara, Masakatsu Shibasaki

    BULLETIN OF THE KOREAN CHEMICAL SOCIETY   Vol. 31 ( 3 ) page: 588 - 594   2010.3

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    Two types of resin-conjugated Tamiflu analogs were synthesized by modifying our original synthetic route of oseltamivir phosphate (Tamiflu). The prepared resins bound to influenza virus neuraminidase, the main target of Tamiflu. The resins will be useful for isolating and identifying presumed endogenous vertebrate proteins that interact with Tamiflu, which might relate to the rarely observed abnormal behavior exhibited by some influenza patients treated with Tamiflu.

    DOI: 10.5012/bkcs.2010.31.03.588

    Web of Science

  36. Design and synthesis of immobilized Tamiflu analog on resin for affinity chromatography Reviewed

    Yasuaki Kimura, Kenzo Yamatsugu, Motomu Kanai, Noriko Echigo, Takashi Kuzuhara, Masakatsu Shibasaki

    TETRAHEDRON LETTERS   Vol. 50 ( 26 ) page: 3205 - 3208   2009.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:PERGAMON-ELSEVIER SCIENCE LTD  

    A resin linked with the Tamiflu core was synthesized by modifying our original synthetic route Of oseltamivir phosphate (Tamiflu). The prepared resin bound to the influenza virus enzyme neuraminidase, the main target of Tamiflu. The immobilized Tamiflu analog will be useful for isolating and identifying presumed endogenous vertebrate proteins that interact with Tamiflu, which might relate to the abnormal behavior exhibited by some influenza patients treated with Tamiflu. (C) 2009 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.tetlet.2009.01.142

    Web of Science

  37. A Synthesis of Tamiflu by Using a Barium-Catalyzed Asymmetric Diels-Alder-Type Reaction Reviewed

    Kenzo Yamatsugu, Liang Yin, Shin Kamijo, Yasuaki Kimura, Motomu Kanai, Masakatsu Shibasaki

    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION   Vol. 48 ( 6 ) page: 1070 - 6   2009

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-V C H VERLAG GMBH  

    DOI: 10.1002/anie.200804777

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MISC 5

  1. Development of glutathione S-transferase (GST) covalent inhibitor International journal

    Shishido Yuko, Tomoike Fumiaki, Kimura Yasuaki, Kuwata Keiko, Yano Takato, Fukui Kenji, Fujikawa Haruka, Sekido Yoshitaka, Murakami-Tonami Yuko, Kameda Tomoshi, Shuto Satoshi, Abe Hiroshi

    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY   Vol. 255   page: .   2018.3

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    Language:English   Publishing type:Research paper, summary (national, other academic conference)  

  2. RETFプローブを用いた生体内の核酸検出

    友池史明, 山岡和樹, 伊藤真央, 木村康明, 井上貴文, 阿部洋

    日本化学会春季年会講演予稿集(CD-ROM)   Vol. 98th   2018

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  3. グルタチオン-S-トランスフェラーゼを標的とした共有結合性阻害剤の開発 International journal

    宍戸 裕子, 藤川 遥加, 友池 史明, 木村 康明, 桑田 啓子, 村上 優子, 福井 健二, 関戸 好孝, 矢野 貴人, 周東 智, 阿部 洋

    生命科学系学会合同年次大会   Vol. 2017年度   page: [3P - 0205]   2017.12

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    Language:Japanese   Publishing type:Research paper, summary (national, other academic conference)   Publisher:生命科学系学会合同年次大会運営事務局  

  4. 共有結合型グルタチオンS-転移酵素阻害剤の創薬研究 International journal

    宍戸 裕子, 藤川 遥加, 木村 康明, 友池 史明, 桑田 啓子, 矢野 貴人, 福井 健二, 関戸 好孝, 村上 優子, 周東 智, 阿部 洋

    日本薬学会年会要旨集   Vol. 137年会 ( 2 ) page: 68 - 68   2017.3

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  5. オセルタミビルによるモノアミン酸化酵素(MAO)阻害活性の検討

    ISODA YUMIKO, HIASA MIKI, KISHIMOTO YASUSHI, SAITO KENTA, KIMURA YASUAKI, KANAI MOTOMU, SHIBASAKI MASAKATSU, KIRINO YUTAKA, HATAKEYAMA HIROSHI, KUZUHARA TAKASHI

    日本薬学会年会要旨集(CD-ROM)   Vol. 133rd ( 3 ) page: ROMBUNNO.29T-PM11S - 155   2013.3

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    Language:Japanese   Publisher:(公社)日本薬学会  

    J-GLOBAL

KAKENHI (Grants-in-Aid for Scientific Research) 9

  1. ジスルフィドを利用したオリゴ核酸デリバリー法の深化と技術拡張

    Grant number:22H02219  2022.4 - 2026.3

    科学研究費助成事業  基盤研究(B)

    木村 康明

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    Authorship:Principal investigator 

    Grant amount:\17160000 ( Direct Cost: \13200000 、 Indirect Cost:\3960000 )

  2. Molecular design strategy to avoid side effects of covalent drugs

    Grant number:20K21249  2020.7 - 2022.3

    Grant-in-Aid for Challenging Research (Exploratory)

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\6500000 ( Direct Cost: \5000000 、 Indirect Cost:\1500000 )

  3. Development of covalent drugs activatable by the target enzymes

    Grant number:18K14356  2018.4 - 2020.3

    Grant-in-Aid for Early-Career Scientists

    Kimura Yasuaki

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    A covalent drug is a drug molecule that forms a covalent bond with a target enzyme to inhibit its function, and has high inhibitory activity. Due to this property, covalent drugs targeting various enzymes have been developed in recent years. However, covalent drugs often form covalent bonds with non-targeting proteins, and side effects derived from them are a major issue in the development of covalent drugs. In this research, as a strategy to avoid such side effect problems, we developed a covalent drug that is activated by a target enzyme and developed an antiviral drug by using a nucleoside analog as an example. The developed nucleoside analog showed good pharmacological activity against HIV.

  4. 標的酵素で活性化される共有結合医薬の開発

    2018.4 - 2020.3

    日本学術振興会  科学研究費補助金 若手研究 

    木村康明

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    Authorship:Principal investigator  Grant type:Competitive

  5. Improvement of catalytic turnover based on transition state control of oligonucleotide template chemical reaction

    Grant number:16KT0052  2016.7 - 2019.3

    Abe Hiroshi

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    The fluorescence reaction based on the oligonucleotide (ON) template reaction is one of the most basic working principles of the RNA detection probe. In this method, an ON probe having a reactive functional group and an ON probe having a fluorescent precursor whose fluorescence is suppressed by a protecting group are associated on the target RNA, and then the protective group is removed and fluorescence signal is generated. Since this fluorescence reaction specifically occurs in the presence of target RNA, it can be the working principle RNA detection probe. In order to detect intracellular RNA highly sensitively, we worked on (1) accelerating ON template reaction and (2) development of a new method of intracellular administration of ON probe without lipofection. Prospective results were obtained in (1) by appropriately selecting the nucleophile for the reaction, and in (2) by use of phosphorothioate in the ON probe.

  6. mRNAの化学合成を可能にするRNAライゲーション反応の開発

    2016.4 - 2018.3

    科学研究費補助金  若手研究(B)

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    Authorship:Principal investigator 

  7. Development of Chemical Ligation Reaction of RNA for Chemical Synthesis of mRNA

    Grant number:16K21091  2016.4 - 2018.3

    Kimura Yasuaki

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\3900000 ( Direct Cost: \3000000 、 Indirect Cost:\900000 )

    We developed chemical ligation reaction for oligonucleotides (ONs) that enables the synthesis of long ONs such as mRNA etc. In the ON synthesis for ON medicines, chemical synthesis is optimal because high molecular homogeneity and tolerance for unnatural structure are required, but the current solid phase synthesis has an upper limit on the length of the products. Therefore, it is necessary to couple the fragments obtained by the solid phase synthesis by chemical reaction. We developed new chemical ligation reactions for ONs, which afford ligated strands having a linkage structure similar to that of natural ONs.

  8. mRNAの化学合成を可能にするRNAライゲーション反応の開発

    2016.4 - 2018.3

    日本学術振興会  科学研究費補助金 若手研究(B) 

    木村康明

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    Authorship:Principal investigator  Grant type:Competitive

  9. 環境調和型触媒的不斉炭素-炭素結合形成反応の開発と重要医薬品合成への応用

    2010.4 - 2013.3

    日本学術振興会  特別研究員奨励費 (DC1) 

    木村康明

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    Authorship:Principal investigator  Grant type:Competitive

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