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Structural analysis of bafilomycin bound to V-ATPase for elucidating its inhibition mechanism based on synthetic chemistry

Research Project

Project/Area Number 15K01821
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Chemical biology
Research InstitutionOsaka University

Principal Investigator

Tsuchikawa Hiroshi  大阪大学, 理学研究科, 助教 (30460992)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsバフィロマイシン / ATPアーゼ / フッ素標識 / 化学合成 / 構造解析 / 固体NMR / V-ATPase / Bafilomycin / F-NMR
Outline of Final Research Achievements

The structural analysis of bafilomycin (Baf), a specific inhibitor towards vacuolar-type ATPase (V-ATPase), was performed based on synthetic chemistry. First, the preparation of bioactive 19F-labelled Baf required for solid-state NMR measurement was achieved by synthesizing several Baf derivatives and evaluating their V-ATPase inhibitory effect. Next, behavior analysis of active and inactive F-Baf derivatives in model membrane resulted in finding the remarkable difference of their mobility, which may probably relate to the difference of their activity. Moreover, a large-scale preparation of V-ATPase as proteoliposomes was successfully accomplished and the structural analysis of F-Baf bound to V-ATPase was examined by solid-state NMR.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (6 results)

All 2018 2017 2016 2015

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Acknowledgement Compliant: 1 results) Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Stereoselective Construction of Cisoidal Bisspiroacetal Frameworks through Magnesium Coordination of the Bilateral Acetal Oxygen Atoms2018

    • Author(s)
      Yoshifumi Yasukawa, Hiroshi Tsuchikawa, Yasuto Todokoro, and Michio Murata
    • Journal Title

      Asian Journal of Organic Chemistry

      Volume: - Issue: 6 Pages: 1101-1106

    • DOI

      10.1002/ajoc.201800074

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bafilomycin analogue site-specifically fluorinated at the pharmacophore macrolactone ring has potent vacuolar-type ATPase inhibitory activity2016

    • Author(s)
      Hiroshi Tsuchikawa, Tatsuru Hayashi, Hajime Shibata, Michio Murata, Yoko Nagumo, Takeo Usui
    • Journal Title

      Tetrahedron Lett

      Volume: 57 Issue: 22 Pages: 2426-2429

    • DOI

      10.1016/j.tetlet.2016.04.075

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Elucidation of Bafilomycin-Vacuolar-type ATPase interaction based on solid-state NMR2018

    • Author(s)
      Tatsuru Hayashi, Hiroshi Tsuchikawa, Yuichi Umegawa, Michio Murata, Yoko Nagumo, Takeo Usui
    • Organizer
      日本化学会 第98春季年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Investigation of the Interaction between Vacuolar-type ATPase and Bafilomycin by Solid-state NMR2017

    • Author(s)
      Hayashi, T, Tsuchikawa, H, Shibata, H, Murata, M, Nagumo, Y, Usui, T
    • Organizer
      18th Tetrahedron Symposium Asia Edition
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 固体NMRによる配座解析を目指したフッ素標識化バフィロマイシンの合成と生物活性評価2016

    • Author(s)
      ○林 達・柴田 一・土川 博史・村田 道雄・臼井 健郎
    • Organizer
      日本化学会 第96春季年会
    • Place of Presentation
      同志社大学 京田辺キャンパス
    • Year and Date
      2016-03-24
    • Related Report
      2015 Research-status Report
  • [Presentation] Design, synthesis and biological evaluation of fluorinated bafilomycin analogues as an NMR probe to analyze the interaction with vacuolar-type ATPase2015

    • Author(s)
      H. Tsuchikawa, H. Shibata, T. Hayashi, S, Hanashima, N. Matsumori, M. Murata, T. Usui
    • Organizer
      PACIFICHEM 2015
    • Place of Presentation
      Honolulu, Hawaii, USA
    • Year and Date
      2015-12-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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