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Challenges to create natural product-drug conjugate starting from screening of natural products that bind to membrane proteins

Research Project

Project/Area Number 22K19115
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 37:Biomolecular chemistry and related fields
Research InstitutionKyushu University

Principal Investigator

Matsumori Nobuaki  九州大学, 理学研究院, 教授 (50314357)

Project Period (FY) 2022-06-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords膜タンパク質 / 脂質 / 天然物 / 相互作用 / 金ナノ粒子 / 親和性 / 薬物 / 低分子薬剤 / 創薬
Outline of Research at the Start

化合物ライブラリーを利用した創薬研究は、目的とする生理活性を有する化合物をいかに探索するかに主眼が置かれてきた。本提案では生理活性を指標とせず、標的膜タンパク質との強い親和性を有する天然物を探索する。ここで応募者の開発した膜タンパク質親和性天然物探索法を活用する。このようにして得られた天然物を起点として、その親和性を保ちつつ、抗体-薬物複合体のように低分子薬剤を結合させる。これにより、高い標的特異性と薬理活性を併せ持つ画期的な新薬を開発する創薬戦略を提案する。このように本研究は、申請者の開発した独自技術を起点とした「天然物-薬物複合体」医薬の創成と、それに基づく新たな創薬分野開拓を目指す。

Outline of Final Research Achievements

This research aims to create “natural product-drug conjugate", starting from our original technology. We have established a technique for stably immobilizing membrane proteins on the surface of gold nanoparticles coated with a thin lipid film. Furthermore, by utilizing this technique, we have developed an experimental scheme to recover membrane protein-binding natural products from a mixture of natural lipids and natural organic compounds, and to detect them by LC-MS. This method made it possible to efficiently obtain natural products with high affinity for membrane proteins.
At the same time, a new method for detection of natural products with high affinity for membrane proteins using the strong red color of gold nanoparticles was also developed. By applying this method to compound libraries immobilized on micro-arrays, the screening of natural products having high affinity to membrane proteins can be made more efficient.

Academic Significance and Societal Importance of the Research Achievements

化合物ライブラリーを利用した創薬研究は、目的とする生理活性を有する化合物をいかに探索するかに主眼が置かれてきた。本研究では生理活性を指標とせず、標的膜タンパク質との強い親和性を有する天然物を探索する。ここで代表者の開発した膜タンパク質親和性天然物探索法を活用する。このようにして得られた天然物を起点として、その親和性を保ちつつ、抗体-薬物複合体のように低分子薬剤を結合させる。これにより、高い標的特異性と薬理活性を併せ持つ画期的な新薬を開発する創薬戦略が実現する。本研究ではこの「天然物-薬物複合体」医薬創成の目途を立てることができ、新たな創薬分野開拓への重要な端緒となった。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (22 results)

All 2024 2023 2022 Other

All Journal Article (10 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 10 results,  Open Access: 7 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 5 results) Remarks (7 results)

  • [Journal Article] Gold nanoparticle-powered screening of membrane protein-specific lipids from complex lipid mixtures2024

    • Author(s)
      Wangamnuayporn Supakorn、Kinoshita Masanao、Kawai Takayuki、Matsumori Nobuaki
    • Journal Title

      Analytical Biochemistry

      Volume: 687 Pages: 115447-115447

    • DOI

      10.1016/j.ab.2023.115447

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Truncated derivatives of amphidinol 3 reveal the functional role of polyol chain in sterol-recognition and pore formation.2024

    • Author(s)
      Nobuaki Matsumori, Manami Hieda, Masayuki Morito, Yuma Wakamiya, Tohru Oishi
    • Journal Title

      Bioorg. Med. Chem. Lett.

      Volume: 98 Pages: 129594-129594

    • DOI

      10.1016/j.bmcl.2023.129594

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cardiolipin binding enhances KcsA channel gating via both its specific and dianion-monoanion interchangeable sites2023

    • Author(s)
      Iwamoto Masayuki、Morito Masayuki、Oiki Shigetoshi、Nishitani Yudai、Yamamoto Daisuke、Matsumori Nobuaki
    • Journal Title

      iScience

      Volume: 26 Issue: 12 Pages: 108471-108471

    • DOI

      10.1016/j.isci.2023.108471

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Variational autoencoder-based chemical latent space for large molecular structures with 3D complexity2023

    • Author(s)
      Ochiai Toshiki、Inukai Tensei、Akiyama Manato、Furui Kairi、Ohue Masahito、Matsumori Nobuaki、Inuki Shinsuke、Uesugi Motonari、Sunazuka Toshiaki、Kikuchi Kazuya、Kakeya Hideaki、Sakakibara Yasubumi
    • Journal Title

      Communications Chemistry

      Volume: 6 Issue: 1 Pages: 249-249

    • DOI

      10.1038/s42004-023-01054-6

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular substructure of the liquid-ordered phase formed by sphingomyelin and cholesterol: sphingomyelin clusters forming nano-subdomains are a characteristic feature2022

    • Author(s)
      Murata Michio、Matsumori Nobuaki、Kinoshita Masanao、London Erwin
    • Journal Title

      Biophysical Reviews

      Volume: 14 Issue: 3 Pages: 655-678

    • DOI

      10.1007/s12551-022-00967-1

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Amphotericin B assembles into seven-molecule ion channels: An NMR and molecular dynamics study2022

    • Author(s)
      Umegawa Yuichi、Yamamoto Tomoya、Dixit Mayank、Funahashi Kosuke、Seo Sangjae、Nakagawa Yasuo、Suzuki Taiga、Matsuoka Shigeru、Tsuchikawa Hiroshi、Hanashima Shinya、Oishi Tohru、Matsumori Nobuaki、Shinoda Wataru、Murata Michio
    • Journal Title

      Science Advances

      Volume: 8 Issue: 24 Pages: 2658-2658

    • DOI

      10.1126/sciadv.abo2658

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inimitable Impacts of Ceramides on Lipid Rafts Formed in Artificial and Natural Cell Membranes2022

    • Author(s)
      Kinoshita Masanao、Matsumori Nobuaki
    • Journal Title

      Membranes

      Volume: 12 Issue: 8 Pages: 727-727

    • DOI

      10.3390/membranes12080727

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Behavior of Triterpenoid Saponin Ginsenoside Rh2 in Ordered and Disordered Phases in Model Membranes Consisting of Sphingomyelin, Phosphatidylcholine, and Cholesterol2022

    • Author(s)
      Garza Darcy Lacanilao、Hanashima Shinya、Umegawa Yuichi、Murata Michio、Kinoshita Masanao、Matsumori Nobuaki、Greimel Peter
    • Journal Title

      Langmuir

      Volume: 38 Issue: 34 Pages: 10478-10491

    • DOI

      10.1021/acs.langmuir.2c01261

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Impact of sphingomyelin acyl chain heterogeneity upon properties of raft-like membranes2022

    • Author(s)
      Hirano Kana、Kinoshita Masanao、Matsumori Nobuaki
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Biomembranes

      Volume: 1864 Issue: 12 Pages: 184036-184036

    • DOI

      10.1016/j.bbamem.2022.184036

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Formation of a Tight Complex between Amphidinol 3 and Sterols in Lipid Bilayers Revealed by Short-Range Energy Transfer2022

    • Author(s)
      Hieda Manami、Tsujimura Koya、Kinoshita Masanao、Matsumori Nobuaki
    • Journal Title

      Bulletin of the Chemical Society of Japan

      Volume: 95 Issue: 12 Pages: 1753-1759

    • DOI

      10.1246/bcsj.20220273

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 潜在空間を構成・検証する生物活性の時空間定量計測手法開発・応用2024

    • Author(s)
      松森信明
    • Organizer
      日本化学会第104春季年会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Ladder-shaped polycyclic ether desulfo-yessotoxin strongly inhibits vacuolar-type ATPase2023

    • Author(s)
      Nobuaki Matsumori
    • Organizer
      ICPAC-Bali 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 脂質機能解明のための多角的分析2022

    • Author(s)
      松森信明
    • Organizer
      第4回脂質駆動学術創生研究部会講演会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 脂質と膜タンパク質の相互作用解析法の開発とその応用2022

    • Author(s)
      松森信明
    • Organizer
      公益財団法人山田科学振興財団 2022年度研究交歓会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Interaction Analysis between Membrane Proteins and Lipids2022

    • Author(s)
      Nobuaki Matsumori
    • Organizer
      ICPAC Kotakinabalu 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] 九州大学大学院理学研究院化学部門生体分析化学研究室

    • URL

      http://www.scc.kyushu-u.ac.jp/BioanalChem/

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
  • [Remarks] Scopus松森信明

    • URL

      https://kyushu-u.elsevierpure.com/ja/persons/nobuaki-matsumori

    • Related Report
      2023 Annual Research Report
  • [Remarks] 研究者情報 松森信明

    • URL

      https://hyoka.ofc.kyushu-u.ac.jp/search/details/K005543/index.html

    • Related Report
      2023 Annual Research Report
  • [Remarks] 九州大学研究者情報 松森信明

    • URL

      https://hyoka.ofc.kyushu-u.ac.jp/search/details/K005543/index.html

    • Related Report
      2022 Research-status Report
  • [Remarks] 研究者プロファイリングツール 九州大学Pure

    • URL

      https://kyushu-u.pure.elsevier.com/ja/persons/nobuaki-matsumori

    • Related Report
      2022 Research-status Report
  • [Remarks] Researchgate

    • URL

      https://www.researchgate.net/profile/Nobuaki-Matsumori

    • Related Report
      2022 Research-status Report
  • [Remarks] Google Scholar

    • URL

      https://scholar.google.com/citations?user=AnjK8JQAAAAJ&hl=en&oi=ao

    • Related Report
      2022 Research-status Report

URL: 

Published: 2022-07-05   Modified: 2025-01-30  

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