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Rational design of synthetic mid-sized agents that disrupt protein-protein interactions

Research Project

Project/Area Number 25288076
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Bio-related chemistry
Research InstitutionKyoto University

Principal Investigator

Ohkanda Junko  京都大学, 化学研究所, 准教授 (50233052)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2015: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2013: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywordsたんぱく質間相互作用 / 阻害剤 / 化学プローブ / 中分子 / K-Ras / フシコクシン / 14-3-3たんぱく質 / 14-3-3 / K-Rasたんぱく質
Outline of Final Research Achievements

Protein-protein interactions (PPIs) play a central role in the signaling pathways that regulate many cellular functions including proliferation, differentiation, and cell death, and have emerged as a new potential clinical targets in the post-genome era. In this study, we aimed to develop a series of mid-sized molecules, of which the molecular size roughly ranges from 600 to 2,000, to recognize the large and flat interfaces and disrupt and detect intracellular PPIs. The cell-permeable bivalent inhibitors of K-Ras-PPIs and the natural product-based fluorescent probes that detect interactions of 14-3-3 and the phospholigands were designed and evaluated in vitro and in cells.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (39 results)

All 2016 2015 2014 2013 Other

All Int'l Joint Research (1 results) Journal Article (9 results) (of which Peer Reviewed: 7 results) Presentation (26 results) (of which Int'l Joint Research: 6 results,  Invited: 19 results) Remarks (3 results)

  • [Int'l Joint Research] University of South Florida(米国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Intracellular generation of a diterpene-peptide conjugate that inhibits 14-3-3-mediated interactions.2015

    • Author(s)
      Parvatkar P., Kato N., Uesugi M., Sato S., Ohkanda J.
    • Journal Title

      J. Am. Chem. Soc.

      Volume: 137 Issue: 50 Pages: 15624-15627

    • DOI

      10.1021/jacs.5b09817

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Manifesting chemical biology in Manila2014

    • Author(s)
      T. Suzuki, J. Ohkanda, T. Mori, M. Nakashima, M. Uesugi
    • Journal Title

      Biochem. J.

      Volume: 464 Issue: 1 Pages: 1-3

    • DOI

      10.1042/bj20140874

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RNA-directed amino acid coupling as a model reaction for primitive coded translation2014

    • Author(s)
      Harada, K., Aoyama, S., Matsugami, A., Kumar, P.K.R., Katahira, M., Kato, N. and Ohkanda, J.
    • Journal Title

      ChemBioChem

      Volume: 未定 Issue: 6 Pages: 794-798

    • DOI

      10.1002/cbic.201400029

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] タンパク質間相互作用を阻害・検出する合成分子の創製2014

    • Author(s)
      大神田淳子
    • Journal Title

      ファルマシア

      Volume: 50 Pages: 1101-1106

    • NAID

      130005265998

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ペプチドミメティクス化2014

    • Author(s)
      大神田淳子
    • Journal Title

      ファルマシア

      Volume: 50 Pages: 1128-1128

    • NAID

      130005265990

    • Related Report
      2014 Annual Research Report
  • [Journal Article] 植物毒から得られる抗がん剤:その作用機序の解明に向けて2014

    • Author(s)
      大神田淳子
    • Journal Title

      黄檗

      Volume: 40 Pages: 13-13

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Module assembly for designing multivalent mid-sized inhibitors of protein-protein interactions2013

    • Author(s)
      Junko Ohkanda
    • Journal Title

      The Chemical Record

      Volume: 13 Issue: 6 Pages: 561-575

    • DOI

      10.1002/tcr.201300026

    • NAID

      120005646493

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chemical ligation of epoxide-containing fusicoccins and peptide fragments guided by 14-3-3 protein2013

    • Author(s)
      Toshio Maki, Akie Kawamura, Nobuo Kato, Junko Ohkanda
    • Journal Title

      Mol. BioSyst.

      Volume: 9 Issue: 5 Pages: 940-943

    • DOI

      10.1039/c3mb90009f

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Peptidomimetic modification improves cell permeation of bivalent farnesyltransferase inhibitors2013

    • Author(s)
      S. Machida, M. Tsubamoto, N. Kato, K.Harada, J. Ohkanda
    • Journal Title

      Bioorganic Medicinal Chemistry

      Volume: (in press) Issue: 14 Pages: 4004-4010

    • DOI

      10.1016/j.bmc.2012.09.061

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] たんぱく質間相互作用を調節する合成分子を創る2016

    • Author(s)
      大神田淳子
    • Organizer
      香川大学2015年度学内講演会
    • Place of Presentation
      香川大学
    • Year and Date
      2016-02-17
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 細胞内たんぱく質間相互作用を制御する中分子の創製2016

    • Author(s)
      大神田淳子
    • Organizer
      お茶の水女子大学化学科公開セミナー
    • Place of Presentation
      お茶の水女子大学
    • Year and Date
      2016-02-12
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Module-assembly for intracellular generation of mid-sized agents2016

    • Author(s)
      J. Ohkanda
    • Organizer
      Asian Chemical Biology Initiative
    • Place of Presentation
      Jakarta, Indonesia
    • Year and Date
      2016-01-30
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Module-Assembly for Mid-sized Agents that Regulate Intracellular Protein-protein Interactions2016

    • Author(s)
      J. Ohkanda, P. Prakash, M. Uesugi, N. Kato, J. Sun
    • Organizer
      The 8th Takeda Science Foundation Symposium on PharmaSciences
    • Place of Presentation
      Osaka
    • Year and Date
      2016-01-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Molecular mechanism of action of fusicoccin-based antitumor agents2015

    • Author(s)
      J. Ohkanda, A. Kusumoto, C. Wang, S. Sato, P. Parvatkar, M. Uesugi, N. Kato
    • Organizer
      Pacifichem2015
    • Place of Presentation
      Hawaii, USA
    • Year and Date
      2015-12-16
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Structure-based Design of PPI Inhibitors that Disrupt Ras Prenylation2015

    • Author(s)
      J. Ohkanda
    • Organizer
      Pacifichem2015
    • Place of Presentation
      Hawaii, USA
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Rational Design of Peptide-based Agents that Control Intracellular Protein-protein Interactions2015

    • Author(s)
      J. Ohkanda
    • Organizer
      The Seventh Peptide Engineering Meeting PEM7
    • Place of Presentation
      Pune, India
    • Year and Date
      2015-12-05
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Intracellular Generation of Diterpene-Peptide Conjugate that Inhibits 14-3-3 Interactions2015

    • Author(s)
      J. Ohkanda, P Parvatkar, M. Uesugi, N. Kato
    • Organizer
      IKCOC-13
    • Place of Presentation
      Kyoto
    • Year and Date
      2015-11-11
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 細胞内たんぱく質間相互作用を制御する中分子の創製2015

    • Author(s)
      大神田淳子
    • Organizer
      中外製薬鎌倉研究所講演会
    • Place of Presentation
      中外製薬鎌倉研究所
    • Year and Date
      2015-10-07
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 中分子型たんぱく質間相互作用阻害剤の細胞内合成2015

    • Author(s)
      Prakash Parvatkar、加藤 修雄、上杉 志成、大神田 淳子
    • Organizer
      第9回バイオ関連化学シンポジウム
    • Place of Presentation
      熊本大学
    • Year and Date
      2015-09-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] たんぱく質間相互作用を標的とする中分子を創る2015

    • Author(s)
      大神田淳子
    • Organizer
      創薬懇話会
    • Place of Presentation
      徳島
    • Year and Date
      2015-07-02
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 結晶構造に基づくたんぱく質間相互作用阻害剤の設計2015

    • Author(s)
      大神田淳子
    • Organizer
      日本薬学会東海支部特別講演会
    • Place of Presentation
      岐阜薬科大学
    • Year and Date
      2015-05-22
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] モジュール法による中分子設計とたんぱく質間相互作用の制御2015

    • Author(s)
      大神田淳子
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-28
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] たんぱく質間相互作用を制御する細胞透過性中分子を創る2015

    • Author(s)
      大神田淳子
    • Organizer
      天然物ケミカルバイオロジー地区ミニシンポジウム
    • Place of Presentation
      仙台
    • Year and Date
      2015-01-15
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Module-assembled, mid-sized agents for controlling protein-protein interactions2014

    • Author(s)
      J. Ohkanda
    • Organizer
      Department Seminar, National University of Singapore
    • Place of Presentation
      Singapore
    • Year and Date
      2014-12-12
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Fusicoccins: Naturally-occurring stabilizers of protein-protein interactions2014

    • Author(s)
      J. Ohkanda
    • Organizer
      The 4th Asian Chemical Biology Initiative
    • Place of Presentation
      Hangzhou, China
    • Year and Date
      2014-11-24
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Fusicoccins: naturally-occurring stabilizers of protein-protein interactions2014

    • Author(s)
      J. Ohkanda
    • Organizer
      The 3rd International Symposium on Chemical Biology of Natural Products: Target ID and Regulation of Bioactivity
    • Place of Presentation
      Osaka
    • Year and Date
      2014-10-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] Module assembly for mid-sized molecules that disrupt intracellular protein-protein interactions2014

    • Author(s)
      J. Ohkanda
    • Organizer
      Sino-Japan Workshop on Chemical Biology
    • Place of Presentation
      Beijing, China
    • Year and Date
      2014-10-12
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] K-Ras specific inactivation by inhibitors of protein-protein interactions2014

    • Author(s)
      J. Ohkanda, M. Tsubamoto, N. Kato, J. Sun, P. Parvatkar, M. Uesugi
    • Organizer
      Swiss-Japanese Chemical Biology Symposium 2014
    • Place of Presentation
      Bern, Switzerland
    • Year and Date
      2014-10-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] Design of mid-sized molecules that disrupt intracellular protein-protein interactions2014

    • Author(s)
      J. Ohkanda
    • Organizer
      Recent Advances in Nanobiotechnology and Chemical Biology 2014
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2014-08-21
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 細胞内たんぱく質間相互作用(PPIs) を阻害する合成分子の設計2014

    • Author(s)
      大神田淳子
    • Organizer
      分子標的設計創薬研究会
    • Place of Presentation
      大阪
    • Year and Date
      2014-07-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] たんぱく質間相互作用(PPIs)を制御・検出する中分子を創る

    • Author(s)
      大神田淳子
    • Organizer
      日本化学会第94春季年会
    • Place of Presentation
      名古屋大学
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Rational design of fusicoccin-based fluorescent probes for detecting 14-3-3 complexes

    • Author(s)
      Junko Ohkanda
    • Organizer
      2014 Queenstown Molecular Biology Meetings in Shanghai;Drug Discovery and International Collaboration
    • Place of Presentation
      Shanghai
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Module Assembly for Designing Mid-sized Inhibitors of Protein-protein Interactions: Bivalent Dual Inhibitors of Protein Prenyltransferases for Selective Inactivation of K-Ras

    • Author(s)
      Junko Ohkanda
    • Organizer
      The 3nd Asian Chemical Biology Initiative
    • Place of Presentation
      Manila
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] たんぱく質間相互作用(PPIs)を標的とする薬剤設計への挑戦~モジュールアセンブリによるPPIs阻害ならびに検出~

    • Author(s)
      大神田淳子
    • Organizer
      奈良先端科学技術大学院大学光ナノサイエンス特別講義
    • Place of Presentation
      奈良先端科学技術大学院大学
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 中分子によるたんぱく質間相互作用(PPIs)の阻害と検出~K-Ras変異がんに対する薬剤開発ならびに14-3-3標識剤への展開~

    • Author(s)
      大神田淳子
    • Organizer
      日本薬学会九州支部主催特別講演会
    • Place of Presentation
      長崎
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Remarks] The Ohkanda Research Group

    • Related Report
      2015 Annual Research Report
  • [Remarks] The Ohkanda Research Group

    • Related Report
      2014 Annual Research Report
  • [Remarks] The Ohkanda Research Group

    • URL

      http://www.scl.kyoto-u.ac.jp/~johkanda/

    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2022-01-27  

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