• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of Photo-Degradable Molecular Glues for Photo-Control of Intracellular Protein Functions

Research Project

Project/Area Number 18K14353
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 37030:Chemical biology-related
Research InstitutionThe University of Tokyo

Principal Investigator

大黒 耕  東京大学, 大学院工学系研究科(工学部), 助教 (60614360)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Discontinued (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywords分子糊 / 多価相互作用 / タンパク質間相互作用 / 光制御 / 細胞遊走 / siRNA / 組織浸透 / 光分解性 / タンパク質機能 / 細胞
Outline of Annual Research Achievements

グアニジニウムイオンを多数もつデンドリマー「分子糊」に光開裂性スペーサーを組み込んだ「光分解性分子糊」を開発した。この光分解性分子糊がタンパク質表面に強力に接着し、他のタンパク質に対する相互作用を阻害することを見出した。紫外光照射に鋭敏に応答し、分解を受け、タンパク質表面から解離することで、タンパク質間相互作用を光誘起することに成功した。特に、モデルタンパク質として肝細胞増殖因子(HGF)を用い、これに対する受容体タンパク質(c-Met)との相互作用を光制御することで、任意の部位・タイミングにおけるシグナル伝達の活性化にも成功した。HGF/c-Metシグナルの結果として生じる細胞遊走の制御に挑戦し、ミリメートルスケールの分解能でこれを達成した。
タンパク質間相互作用は、多岐にわたる生物現象に関与する重要な生体分子現象であり、これを制御する手法の開拓は、分子生物学・生化学などの基礎的観点のみならず疾患の治療という医学的観点からも重要である。本研究で基盤として用いている分子糊の接着はきわめて普遍性が高く、原理的にあらゆるタンパク質間相互作用に適用可能である。標的とするタンパク質に応じた精密な分子設計が必要な従来のアプローチとは異なり、立体構造が未知なタンパク質をも標的とすることが可能である。

Report

(2 results)
  • 2019 Annual Research Report
  • 2018 Research-status Report
  • Research Products

    (27 results)

All 2019 2018

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (22 results) (of which Int'l Joint Research: 8 results,  Invited: 4 results)

  • [Journal Article] Molecular Glue that Spatiotemporally Turns on Protein?Protein Interactions2019

    • Author(s)
      Rina Mogaki, Kou Okuro, Ryosuke Ueki, Shinsuke Sando, Takuzo Aida
    • Journal Title

      J. Am. Chem. Soc.

      Volume: 141 Issue: 20 Pages: 8035-8040

    • DOI

      10.1021/jacs.9b02427

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transferrin-Appended Nanocaplet for Transcellular siRNA Delivery into Deep Tissues2019

    • Author(s)
      Ai Kohata, P. K. Hashim, Kou Okuro, Takuzo Aida
    • Journal Title

      Journal of the American Chemical Society

      Volume: 141 Issue: 7 Pages: 2862-2866

    • DOI

      10.1021/jacs.8b12501

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Nitrobenzoxadiazole-Appended Cell Membrane Modifiers for Efficient Optoporation with Noncoherent Light2018

    • Author(s)
      Saya Otake, Kou Okuro, Davide Bochicchio, Giovanni M. Pavan, Takuzo Aida
    • Journal Title

      Bioconjugate Chem.

      Volume: 29 Issue: 6 Pages: 2068-2073

    • DOI

      10.1021/acs.bioconjchem.8b00270

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Dendritic Molecular Glues with Reductively Cleavable Guanidinium Ion Pendants: Highly Efficient Intracellular siRNA Delivery via Direct Translocation2018

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

      Chem. Lett.

      Volume: 47 Pages: 1232-1235

    • NAID

      130007472140

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Spatiotemporally Controlled Nuclear Translocation of Guests in Living Cells Using Caged Molecular Glues as Photoactivatable Tags2018

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

      J. Vis. Exp.

      Volume: 143 Issue: 143

    • DOI

      10.3791/58631

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Design and Applicaton of Molecular Glues Based on Multivalent Interactions2019

    • Author(s)
      Kou Okuro
    • Organizer
      日本化学会第99春季年会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Molecular Glues for Control of Biomolecular Functions2019

    • Author(s)
      Kou Okuro
    • Organizer
      日本化学会第99春季年会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 光刺激に応じた細胞内送達を可能にする細胞膜修飾剤の開発2019

    • Author(s)
      大竹沙耶, 大黒 耕, 相田卓三
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 組織深部へのsiRNA送達を実現するタンパク質被覆ナノカプセル2019

    • Author(s)
      木幡 愛, P. K. Hashim, 大黒 耕, 相田卓三
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Supramolecular Polymerization of GroEL Protein and siRNA for 'Artificial Viruses'2019

    • Author(s)
      P. K. Hashim, Seunghyun Sim, Kou Okuro, Takuzo Aida
    • Organizer
      日本化学会第99春季年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Noncovalently Caged Proteins with Molecular Glues2019

    • Author(s)
      Rina Mogaki, Kou Okuro, Takuzo Aida
    • Organizer
      日本化学会第99春季年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 分子糊を用いた生体分子機能制御2018

    • Author(s)
      大黒 耕, 相田卓三
    • Organizer
      第67回高分子年次大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Photoresponsive Molecular Glues for Control of Biomolecular Functions2018

    • Author(s)
      Kou Okuro
    • Organizer
      The 3rd International Conference on Emerging Advanced Nanomaterials 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Photoresponsive Molecular Glues for Control of Biomolecular Functions2018

    • Author(s)
      Kou Okuro
    • Organizer
      The 4th International Congress on Advanced Materials 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Cell Membrane Modifiers for Efficient Optoporation2018

    • Author(s)
      Saya Otake, Kou Okuro, Takuzo Aida
    • Organizer
      The 12th SPSJ International Polymer Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Nanocaplet for siRNA Delivery into Deep Tissues2018

    • Author(s)
      Ai Kohata, P. K. Hashim, Kou Okuro, Takuzo Aida
    • Organizer
      The 12th SPSJ International Polymer Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 木幡 愛, P. K. Hashim, 大黒 耕, 相田卓三2018

    • Author(s)
      木幡 愛, P. K. Hashim, 大黒 耕, 相田卓三
    • Organizer
      第8回CSJフェスタ2018
    • Related Report
      2018 Research-status Report
  • [Presentation] 高効率なオプトポレーションを可能にする細胞膜修飾剤の開発2018

    • Author(s)
      大竹沙耶, 大黒 耕, 相田卓三
    • Organizer
      第12回バイオ関連化学シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] Multifunctional Gold Nanoparticles for Protein Degradation2018

    • Author(s)
      Kiyoshi Morishita, Kou Okuro, Takuzo Aida
    • Organizer
      Gordon Research Conference on Noble Metal Nanoparticles
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Multifunctional Gold Nanoparticles for Protein Degradation2018

    • Author(s)
      Kiyoshi Morishita, Kou Okuro, Takuzo Aida
    • Organizer
      Gordon Research Seminar on Noble Metal Nanoparticles
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Multifunctional Gold Nanoparticles for Protein Degradation2018

    • Author(s)
      Kiyoshi Morishita, Kou Okuro, Takuzo Aida
    • Organizer
      第67回高分子年次大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 標的選択的デリバリーを志向したタンパク質修飾siRNA内包ナノカプセル2018

    • Author(s)
      木幡 愛, P. K. Hashim, 大黒 耕, 相田卓三
    • Organizer
      第67回高分子年次大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Stimuli-responsive Molecular Glues for Manipulation of Biological Events2018

    • Author(s)
      Rina Mogaki, Kou Okuro, Takuzo Aida
    • Organizer
      The 12th SPSJ International Polymer Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Adhesive Photoswitch for Modulation of Protein Functions2018

    • Author(s)
      Rina Mogaki, Kou Okuro, Takuzo Aida
    • Organizer
      2nd International Symposium on Photopharmacology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 生命現象の制御を指向した光応答性分子糊2018

    • Author(s)
      茂垣里奈 , 大黒 耕, 相田卓三
    • Organizer
      第12回バイオ関連化学シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] 生命現象の制御を指向した光応答性分子糊2018

    • Author(s)
      茂垣里奈 , 有坂暁雄, 大黒 耕, 相田卓三
    • Organizer
      日本ケミカルバイオロジー学会第13回年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 生命現象の制御を指向した光応答性分子糊2018

    • Author(s)
      茂垣里奈 , 有坂暁雄, 大黒 耕, 相田卓三
    • Organizer
      第67回高分子年次大会
    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2021-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi