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

2011 Fiscal Year Final Research Report

Protein Knockdown Approach : Hybrid Small Molecules which Induce Proteasome Degradation of Target Proteins

Research Project

  • PDF
Project/Area Number 21651092
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Living organism molecular science
Research InstitutionThe University of Tokyo

Principal Investigator

HASHIMOTO Yuichi  東京大学, 分子細胞生物学研究所, 教授 (90164798)

Co-Investigator(Renkei-kenkyūsha) ISHIKAWA Minoru  東京大学, 分子細胞生物学研究所, 助教 (70526839)
Project Period (FY) 2009 – 2011
Keywords生物活性分子の設計・合成 / タンパク質の自己分解
Research Abstract

Protein knockdown can be achieved by the use of a small molecule that possesses affinity for both the target protein and ubiquitin ligase. As the ubiquitin ligase, we selected cIAP1 which specifically binds methylbestatin. Several hybrid molecules consisting of methylbestatin and a ligand for various proteins were designed and synthesized. These hybrid molecules induced selective decomposition of the target proteins.

  • Research Products

    (16 results)

All 2012 2011 2010 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (11 results) Remarks (1 results)

  • [Journal Article] Development oftarget protein-selective degradation inducerfor protein knockdown2011

    • Author(s)
      Y. Itoh, M. Ishikawa, R. Kitaguchi, S. Sato, M. Naito, Y. Hashimoto
    • Journal Title

      Bioorg. Med. Chem

      Volume: 19 Pages: 3229-3241

    • DOI

      Doi:10.1016/j.bmc.2011.03.057

    • Peer Reviewed
  • [Journal Article] Design, synthesis and biological evaluation of nuclear receptor-degradation inducers2011

    • Author(s)
      Y. Itoh, R. Kitaguchi, M. Ishikawa, M. Naito, Y. Hashimoto
    • Journal Title

      Bioorg. Med. Chem

      Volume: 19 Pages: 6768-6778

    • DOI

      Doi:10.1016/j.bmc.2011.09.041

    • Peer Reviewed
  • [Journal Article] Specific degradation of CRABP-II via cIAP1-mediatd ubiquitylation induced by hybrid molecules that crosslink cIAP1 and the target protein2011

    • Author(s)
      K. Okuhira, N. Ohoka, K. Sai, T. Nishimaki-Mogami, Y. Itoh, M. Ishikawa, Y. Hashimoto, M. Naito
    • Journal Title

      FEBS Lett.

      Volume: 585 Pages: 1147-1152

    • DOI

      Doi:10.1016/j.febslet.2011.03.019

    • Peer Reviewed
  • [Journal Article] Protein knockdown using methyl bestatin-ligand hybrid molecules : design andsynthesis of inducers of ubiquitination-mediated degradation of cellular retinoic acid-binding proteins2010

    • Author(s)
      Y. Itoh, M. Ishikawa, M. Naito, Y. Hashimoto
    • Journal Title

      J. Amer. Chem. Soc

      Volume: 132 Pages: 5820-5826

    • DOI

      DOI:10.1021/ja100691p

    • Peer Reviewed
  • [Presentation] Retinoids as ligands for pharmaceutical chaperone and protein knockdown approach2012

    • Author(s)
      Y. Hashimoto
    • Organizer
      The 1st International Symposium on Latent TGF-βActivation Reaction
    • Place of Presentation
      Kobe
    • Year and Date
      2012-02-25
  • [Presentation] Development of small molecules that induce IAP-mediated ubiquitylation and proteosomal degradation of target protein2012

    • Author(s)
      M. Naito, K. Okuhira, N. Ohoka, N. Shibata, T. Hattori, Y. Itoh, M. Ishikawa, Y. Hashimoto
    • Organizer
      The Sixth International Conference. SUMO, Ubiquitin, UBL Proteins
    • Place of Presentation
      Houston
    • Year and Date
      2012-02-08
  • [Presentation] Protein knockdown : selective degradation of target proteins in cells using methyl bestatin-ligand hybrid molecules2011

    • Author(s)
      M. Ishikawa, Y. Itoh, R. Kitaguchi, S. Sato, M. Naito, Y. Hashimoto
    • Organizer
      AIMECS 2011
    • Place of Presentation
      Tokyo
    • Year and Date
      2011-11-29
  • [Presentation] タンパク質の形と存在状態を狙う生理活性物質の創製2011

    • Author(s)
      橋本祐一
    • Organizer
      平成23年度後期(秋季)有機合成化学講習会
    • Place of Presentation
      東京
    • Year and Date
      2011-11-17
  • [Presentation] 核内受容体を細胞内で選択的に分解誘導する分子の創製2011

    • Author(s)
      北口梨沙、伊藤幸裕、石川稔、内藤幹彦、橋本祐一
    • Organizer
      日本レチノイド研究会第22回学術集会
    • Place of Presentation
      東京
    • Year and Date
      2011-11-11
  • [Presentation] 細胞内に局在するタンパク質を標的としたプロテインノックダウン技術の検討2011

    • Author(s)
      奥平桂一郎、大岡伸通、最上(西巻)知子、橋本祐一、内藤幹彦
    • Organizer
      日本がん分子標的治療学会第15回学術集会
    • Place of Presentation
      東京
    • Year and Date
      2011-06-22
  • [Presentation] プロテインノックダウン法を利用した核内受容体分解誘導低分子の創製2011

    • Author(s)
      北口梨沙、伊藤幸裕、石川稔、内藤幹彦、橋本祐一
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      静岡
    • Year and Date
      2011-03-28
  • [Presentation] Protein knockdown using ubiquitination activity of cIAP1 : Discoveryof CRABP degradation inducers.2010

    • Author(s)
      Y. Itoh, M. Ishikawa, M. Naito, Y. Hashimoto
    • Organizer
      PACIFICHEM 2010
    • Place of Presentation
      Honolulu
    • Year and Date
      2010-12-15
  • [Presentation] プロテインノックダウン法を利用した創薬指向型CRABP分解誘導剤の創製2010

    • Author(s)
      伊藤幸裕、石川稔、奥平桂一郎、内藤幹彦、橋本祐一
    • Organizer
      第29回メディシナルケミストリーシンポジウム
    • Place of Presentation
      京都
    • Year and Date
      2010-11-17
  • [Presentation] 細胞内レチノイド結合タンパク質の分解を誘導するレチノイン酸連結化合物の創製2010

    • Author(s)
      石川稔、伊藤幸裕、内藤幹彦、橋本祐一
    • Organizer
      日本ビタミン学会第62回大会
    • Place of Presentation
      盛岡
    • Year and Date
      2010-06-11
  • [Presentation] プロテインノックダウン法の開発2010

    • Author(s)
      伊藤幸裕、石川稔、内藤幹彦、橋本祐一
    • Organizer
      第8回次世代を担う有機科学シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2010-05-13
  • [Remarks]

    • URL

      http://www.iam.u-tokyo.ac.jp/chem/IMCB-8ken-HP/Index.html

URL: 

Published: 2013-07-31  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi