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Exploration of alpha helix domains for drug target

Research Project

Project/Area Number 26670326
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Hygiene and public health
Research InstitutionThe University of Tokyo

Principal Investigator

Terashima Yuya  東京大学, 医学(系)研究科(研究院), 助教 (90538729)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsGPCR / 創薬標的 / ペプチド / 創薬 / ケモカイン受容体
Outline of Final Research Achievements

The alpha-helix plays an important role for protein-protein interaction and cellular functions. We searched for alpha-helix sequences which serve as a drug target as well as an inhibition tool for the target function by its synthesized peptide of the corresponding sequence with the membrane permeable property. We identified two peptides which inhibit cellular chemotaxis when combined with the membrane permeable sequence. The fact that one amino-acid substitution with hydrophobic residue substantially enhanced its inhibition ability indicates that it functions inside the cell and its hydrophobicity is important for its ability to inhibit chemotaxis. The strategy established in this study can be applicable for broad target proteins and the identified peptides are promising therapeutic tool to inhibit disease-related chemotaxis.

Report

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

    (8 results)

All 2015 2014

All Journal Article (5 results) (of which Peer Reviewed: 4 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] ケモカインシグナル2015

    • Author(s)
      遠田悦子、寺島裕也、松島綱治
    • Journal Title

      生体の科学

      Volume: 66 Pages: 412-413

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Robust anti-tumor effects of combined anti-CD4 depleting antibody and anti-PD-1/PD-L1immune checkpoint antibody treatment in mice.2015

    • Author(s)
      Ueha S, Yokochi S, Ishiwata Y, Ogiwara H, Chand K, Nakajima T, Hachiga K,Shichino S, Terashima Y, Toda E, Shand FH, Kakimi K, Ito S, Matshushima K.
    • Journal Title

      Cancer Immunol Res.

      Volume: Epub ahead of print Issue: 6 Pages: 631-640

    • DOI

      10.1158/2326-6066.cir-14-0190

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Robust anti-tumor effects of combined anti-CD4 depleting antibody and anti-PD-1/PD-L1 immune checkpoint antibody treatment in mice.2015

    • Author(s)
      Ueha S, Yokochi S, Ishiwata Y, Ogiwara H, Chand K, Nakajima T, Hachiga K, Shichino S, Terashima Y, Toda E, Shand FH, Kakimi K, Ito S, Matshushima K.
    • Journal Title

      Cancer Immunol Res.

      Volume: 印刷中

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Structural basis for the binding of the membrane-proximal C-terminal region of chemokine receptor CCR2 with the cytosolic regulator FROUNT2014

    • Author(s)
      Esaki K, Yoshinaga S, Tsuji T, Toda E, Terashima Y, Saitoh T, Kohda D, Kohno T, Osawa M, Ueda T, Shimada I, Matsushima K, Terasawa H
    • Journal Title

      FEBS J

      Volume: 281 Issue: 24 Pages: 552-566

    • DOI

      10.1111/febs.13096

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Identification of a binding element for the cytoplasmic regulator FROUNTin the membrane-proximal C-terminal region of chemokine receptors CCR2 and CCR5.2014

    • Author(s)
      Toda E, Terashlma Y, Esakii K, Yoshinaga S, Sugihara M, Kofuku Y, Shimada I, Suwa M, Kanegasaki S, Terasawa H, Matsushima K.
    • Journal Title

      Biochemical Journal

      Volume: Vol.457 Issue: 2 Pages: 313-322

    • DOI

      10.1042/bj20130827

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] A chemokine receptor-associating molecule FROUNT is required for macrophage infiltraion and tumor progression.2015

    • Author(s)
      Yuya Terashima, Etsuko Toda, and Kouji Matsushima
    • Organizer
      International Conference of Cancer Immunotherapy and Macrophages (ICCIM) 2015
    • Place of Presentation
      Tokyo
    • Year and Date
      2015-07-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Intracellular blockade of chemotaxis via targeting GPCR helix8-associating molecule FROUNT2015

    • Author(s)
      Yuya Terashima, Etsuko Toda, and Kouji Matsushima
    • Organizer
      Keystone Synposia; The Biological Code of Cell Signaling
    • Place of Presentation
      Steamboat Springs, Colorado USA
    • Year and Date
      2015-01-01 – 2015-01-16
    • Related Report
      2014 Research-status Report
  • [Presentation] A chemokine receptor-associating molecule, FROUNT is required for tumor metastasis by regulating tumor microenvironment2014

    • Author(s)
      Yuya Terashima and Kouji Matsushima
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report

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

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