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SUMO:SBMのタンパク質 - タンパク質相互作用阻害剤の発見

Research Project

Project/Area Number 12F02509
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section外国
Research Field ケミカルバイオロジー
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

VOET ARNOUT (2013)  独立行政法人理化学研究所, ライフサイエンス技術基盤研究センター, 国際特別研究員

ZHANG Kam (2012)  独立行政法人理化学研究所, Zhang独立主幹研究ユニット, ユニットリーダー

Co-Investigator(Kenkyū-buntansha) VOET Arnout  独立行政法人理化学研究所, Zhang独立主幹研究ユニット, 外国人特別研究員
Project Period (FY) 2012 – 2014-03-31
Project Status Declined (Fiscal Year 2013)
Budget Amount *help
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2013: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2012: ¥800,000 (Direct Cost: ¥800,000)
KeywordsSUMO-SIM / Inhibitor / In Silico / ALPHAscreen / NMR / EleKit / SUMO-SBM / バーチャルスクリーニング / Poisson-Boltzmann
Research Abstract

Since the start of this project we have developed a computational approach to efficiently target protein-protein interactions, currently a hot topic in drug discovery. The sumo-sim interaction is essential in sumoylation and remains poorly understood. Therefore there is a need for a chemical probe to investigate this interaction. We have demonstrated the feasibility to target the SUMO-SIM interaction with druglike compounds for PPI inhibition as well as stimulation. These results have been published into 2 different publications. Given these promising results and after the development of the assays, a medium throughput screening experiment was set up and novel classes of compounds were identified that have possibly a more promising future for clinical usage. While this project is now terminated, it has opened a path to future research efforts as these compounds are interesting for optimization to analyse the sumo-SIM interactions and evaluate clinical usage (chemo and radio sensitization of cancer cells).
Furthermore parallel with this research a novel method to utilize electrostatics for drug discovery targeting protein-protein interactions was developed and evaluated. This new method was also employed during the SAMPL4 virtual screening challenge and helped in obtained the highest ranking score.

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

everything went as anticipated.

Strategy for Future Research Activity

This research project has now been terminated as the research fellow changed to a RIKEN FPR fellowship.

Report

(2 results)
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (5 results)

All 2014 2013

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (2 results) (of which Invited: 1 results)

  • [Journal Article] Combining in silico and in cerebro approaches for virtual screening and pose prediction in SAMPL42014

    • Author(s)
      Voet AR, Kumar A, Berenger F, Zhang KY.
    • Journal Title

      Journal Computer Aided Molecular Design

      Volume: (In press)

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Assay methods for small ubiquitin-like modifier (SUMO)-SUMO-interacting motif (SIM) interactions in vivo and in vitro using a split-luciferase complementation system2014

    • Author(s)
      Hirohama M, Voet AR, Ozawa T, Saitoh H, Nakao Y, Zhang KY, Ito A, Yoshida M.
    • Journal Title

      Anal Biochem.

      Volume: 448 Pages: 92-4

    • DOI

      10.1016/j.ab.2013.12.009

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Electrostatic similarities between protein and small molecule ligands facilitate the desien of protein-protein interaction inhibitors.2013

    • Author(s)
      Voet A, Berenger F, Zhang KY.
    • Journal Title

      Plos One

      Volume: 8 Issue: 10 Pages: e75762-e75762

    • DOI

      10.1371/journal.pone.0075762

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Computational methods for the inhibition of SMPPII2013

    • Author(s)
      Arnout Voet
    • Organizer
      European Workshop in Drug Discovery
    • Place of Presentation
      Siena : Certosa di Pontig nano (Italy)
    • Year and Date
      2013-05-24
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Computational Methods for the discovery of SMPPII2013

    • Author(s)
      Arnout R. D Voet
    • Organizer
      Drug Discovery Chemistry
    • Place of Presentation
      Munich, Germany(招待講演)
    • Related Report
      2012 Annual Research Report

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Published: 2013-04-25   Modified: 2024-03-26  

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