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Universal Methodology for Drug Development Based on Stimuli-responsive Molecular Glues

Research Project

Project/Area Number 26810046
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Functional solid state chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

Okuro Kou  東京大学, 工学(系)研究科(研究院), 助教 (60614360)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords分子糊 / 刺激応答性 / 光重合 / siRNA / ATP / 酵素阻害剤 / 酵素 / 鋳型重合 / タンパク質 / 酵素阻害 / 結合力の増強
Outline of Final Research Achievements

By conjugation of a molecular glue with an enzyme inhibitor, >30-times binding affinity and >10-times inhibitory effect were achieved. The results support the concept that drug efficacy can be enhanced by simply introducing an “adhesive" moiety. In this research project, we had mainly focused on development of stimuli-responsive molecular glues, though different from the original plan, and succeeded in synthesis of “photo-polymerizable”, “redox-responsive”, and “ATP-binding” molecular glues. Each of the molecular glues demonstrates a remarkable properties to manipulate biological functions. The development of new stimuli-responsive molecular glues will definitely promote the project toward treatment of unmet-needs diseases.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (22 results)

All 2016 2015 2014

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Acknowledgement Compliant: 3 results,  Open Access: 1 results) Presentation (18 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Photoinduced Bioorthogonal 1,3-Dipolar Polycycloaddition Promoted by Oxianionic Substrates for Spatiotemporal Operation of Molecular Glues2016

    • Author(s)
      Junichi Hatano, Kou Okuro, Takuzo Aida
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 55 Issue: 1 Pages: 193-198

    • DOI

      10.1002/anie.201507987

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Boronic Acid–Appended Molecular Glues for ATP-Responsive Activity Modulation of Enzymes2016

    • Author(s)
      Kou Okuro, Mizuki Sasaki, Takuzo Aida
    • Journal Title

      J. Am. Chem. Soc.

      Volume: 138 Issue: 17 Pages: 5527-5530

    • DOI

      10.1021/jacs.6b02664

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Reductively Cleavable Nanocaplets for siRNA Delivery by Template-Assisted Oxidative Polymerization2015

    • Author(s)
      P. K. Hashim, Kou Okuro, Shigekazu Sasaki, Yasutaka Hoashi, Takuzo Aida
    • Journal Title

      J. Am. Chem. Soc.

      Volume: 137 Issue: 50 Pages: 15608-15611

    • DOI

      10.1021/jacs.5b08948

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Molecular Glues for Manipulating Enzymes : Trypsin Inhibition by Benzamidine-Conjugated Molecular Glues2015

    • Author(s)
      Rina Mogaki, Kou Okuro, Takuzo Aida
    • Journal Title

      Chem. Sci.

      Volume: 6 Issue: 5 Pages: 2802-2805

    • DOI

      10.1039/c5sc00524h

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 生体分子機能の制御を実現する刺激応答性分子糊(1):分子設計戦略2016

    • Author(s)
      茂垣里奈, 大黒 耕, 相田卓三
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学(京都府, 京田辺市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] 生体分子機能の制御を実現する刺激応答性分子糊(2):タンパク質の機能制御2016

    • Author(s)
      茂垣里奈, 大黒 耕, 相田卓三
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学(京都府, 京田辺市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] Development of Adhesive Nanoparticles for Clinical Application2016

    • Author(s)
      鄭 麗華, 大黒 耕, 相田卓三
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学(京都府, 京田辺市)
    • Year and Date
      2016-03-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] Adhesive ATP-Switch for Modulation of Biomolecular Functions2016

    • Author(s)
      大黒 耕, 佐々木みず葵, 相田卓三
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学(京都府, 京田辺市)
    • Year and Date
      2016-03-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] “Caged” molecular glue uncaged by cancer specific signals2015

    • Author(s)
      Chienyu Chen, Junichi Hatano, Kou Okuro, Takuzo Aida
    • Organizer
      環太平洋国際化学会議2015
    • Place of Presentation
      ホノルル, 米国
    • Year and Date
      2015-12-20
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Reductively cleavable Nanocaplets for gene and protein delivery by template assisted oxidative polymerization2015

    • Author(s)
      P. K. Hashim, Kou Okuro, Takuzo Aida
    • Organizer
      The 11th International Conference on Advanced Polymers via Macromolecular Engineering
    • Place of Presentation
      パシフィコ横浜(神奈川県, 横浜市)
    • Year and Date
      2015-10-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 医療への応用を目指した生体分子接着性ナノ粒子の設計2015

    • Author(s)
      鄭 麗華, 大黒 耕, 相田卓三
    • Organizer
      第5回CSJ化学フェスタ2015
    • Place of Presentation
      タワーホール船堀(東京都, 船堀市)
    • Year and Date
      2015-10-14
    • Related Report
      2015 Annual Research Report
  • [Presentation] 癌細胞選択的に接着性を発現するケージド分子糊の設計と合成2015

    • Author(s)
      陳 健宇, 波多野淳一, 大黒 耕, 相田卓三
    • Organizer
      第5回CSJ化学フェスタ2015
    • Place of Presentation
      タワーホール船堀(東京都, 船堀市)
    • Year and Date
      2015-10-13
    • Related Report
      2015 Annual Research Report
  • [Presentation] Self assembly of siRNA embedded protein GroEL for artificial viruses2015

    • Author(s)
      P. K. Hashim, Seunghyun Sim, Kou Okuro, Daigo Miyajima, Takuzo Aida
    • Organizer
      Gordon Research Conference (Artificial Molecular Switches and Motors)
    • Place of Presentation
      イーストン, 米国
    • Year and Date
      2015-06-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Adhesive Photoswitch for Intracellular Control of Protein Functions2015

    • Author(s)
      Rina Mogaki, Kou Okuro, Takuzo Aida
    • Organizer
      Gordon Research Conference (Self-Assembly & Supramolecular Chemistry)
    • Place of Presentation
      ルッカ, イタリア
    • Year and Date
      2015-05-20
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Oxyanionic Template-Assisted Photopolymerization for Site-selective Adhesion of Molecular Glue2015

    • Author(s)
      波多野淳一、大黒 耕、相田卓三
    • Organizer
      日本化学会第95春季年会
    • Place of Presentation
      船橋・千葉
    • Year and Date
      2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] 細胞内でのタンパク質機能制御を実現する接着性光スイッチの開発2015

    • Author(s)
      茂垣里奈、大黒 耕、相田卓三
    • Organizer
      日本化学会第95春季年会
    • Place of Presentation
      船橋・千葉
    • Year and Date
      2015-03-26
    • Related Report
      2014 Research-status Report
  • [Presentation] Photoactivatable Molecular Glues for In Situ Activation of Adhesion2014

    • Author(s)
      波多野淳一、大黒 耕、相田卓三
    • Organizer
      NanoBio Australia 2014
    • Place of Presentation
      ブリスベン・オーストラリア
    • Year and Date
      2014-07-07
    • Related Report
      2014 Research-status Report
  • [Presentation] Affinity Molecular Glue: Adhesion-mediated Enhancement of Ligand-Protein Binding2014

    • Author(s)
      茂垣里奈、大黒 耕、相田卓三
    • Organizer
      NanoBio Australia 2014
    • Place of Presentation
      ブリスベン・オーストラリア
    • Year and Date
      2014-07-07
    • Related Report
      2014 Research-status Report
  • [Presentation] Photoactivatable Molecular Glues for in situ Activation of Adhesion2014

    • Author(s)
      波多野淳一、大黒 耕、相田卓三
    • Organizer
      The 9th International Symposium on Macrocyclic and Supramolecular Chemistry
    • Place of Presentation
      上海・中国
    • Year and Date
      2014-06-07
    • Related Report
      2014 Research-status Report
  • [Presentation] 特定タンパク質を認識するリガンドを導入したアフィニティモレキュラーグルーの開拓2014

    • Author(s)
      茂垣里奈、大黒 耕、相田卓三
    • Organizer
      第63回高分子学会年次大会
    • Place of Presentation
      名古屋国際会議場・名古屋
    • Year and Date
      2014-05-29
    • Related Report
      2014 Research-status Report
  • [Presentation] ケージドモレキュラーグルー:光に応答して接着性を発現する分子糊2014

    • Author(s)
      大黒 耕、有坂暁雄、相田卓三
    • Organizer
      第63回高分子学会年次大会
    • Place of Presentation
      名古屋国際会議場・名古屋
    • Year and Date
      2014-05-28
    • Related Report
      2014 Research-status Report
  • [Presentation] Photo-polymerizable Molecular Glue for Site-selective Adhesion in Cell Engineering2014

    • Author(s)
      波多野淳一、大黒 耕、相田卓三
    • Organizer
      第63回高分子学会年次大会
    • Place of Presentation
      名古屋国際会議場・名古屋
    • Year and Date
      2014-05-28
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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