Rational design of protein-protein interaction inhibitors

• Project/Area Number: 23510277
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical biology
• Research Institution: Kyoto University
• Principal Investigator: SATO Shinichi 京都大学, 物質-細胞統合システム拠点, 助教 (70534478)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: X線結晶構造解析 / ケミカルバイオロジー

Research Abstract

Protein-protein interactions are central to most biological processes and expected to represent an important class of drug targets near future. However, it remains challenging to design small-molecule inhibitors of protein-protein interaction, in part due to the lack of structural information of the small molecule-protein complexes. We recently identified S100 protein as a target protein of wrenchnolol which is a bioactive compound we found. Biological experiment revealed that the wrenchonolol inhibits the protein-protein interaction between S100 protein and its partner protein Annexin. In this project, we identified a crystallization condition of a complex between wrenchnolol and Annexin. Structural determination of the complex would permit the design of new wrenchnolol analogs with better activities.

Research Products

• [Journal Article] A chemical probe that labels human pluripotent stem cells (2014)
  • Author(s): Hirata N., Nakagawa M., Fujibayashi Y., Yamauchi K., Murata A., Minami I., Tomioka M., Kondo T., Kuo T. F., Endo H., Inoue H., Sato S., Ando S., Kawazoe Y., Aiba K., Nagata K., Kawase E., Chang Y. T., Suemori H., Eto K., Nakauchi H., Yamanaka S., Nakatsuji N., Ueda K., Uesugi M.
  • Journal Title: Cell Rep. Volume: 6(6) Pages: 1165-1174
  • NAID: 120005466668
  • Peer Reviewed
• [Journal Article] A chemical probe that labels human pluripotent stem cells (2014)
  • Author(s): Hirata N, Nakagawa M, Fujibayashi Y, Yamauchi K, Murata A, Minami I, Tomioka M, Kondo T, Kuo TF, Endo H, Inoue H, Sato S, Ando S, Kawazoe Y, Aiba K, Nagata K, Kawase E, Chang YT, Suemori H, Eto K, Nakauchi H, Yamanaka S, Nakatsuji N, Ueda K, Uesugi M
  • Journal Title: Cell reports Volume: 6 Issue: 6 Pages: 1165-74
  • DOI: 10.1016/j.celrep.2014.02.006
  • NAID: 120005466668
  • Peer Reviewed / Open Access
• [Journal Article] Small molecule-induced clustering of heparan sulfate promotes cell adhesion (2013)
  • Author(s): Takemoto, N., Suehara, T., Frisco, H. L., Sato, S., Sezaki, T., Kusamori, K., Kawazoe, Y., Park, S. M., Yamazoe, S., Mizuhata, Y., Inoue, R., Miller, G. J., Hansen, S. U., Jayson, G. C., Gardiner, J. M., Kanaya, T., Tokitoh, N., Ueda, K., Takakura, Y., Kioka, N., Nishikawa, M., and Uesugi, M.
  • Journal Title: J. Am. Chem. Soc. Volume: 135(30) Pages: 11032-11039
  • Peer Reviewed
• [Journal Article] Small-molecule-induced clustering of heparan sulfate promotes cell adhesion (2013)
  • Author(s): Takemoto N, Suehara T, Frisco HL, Sato S, Sezaki T, Kusamori K, Kawazoe Y, Park SM, Yamazoe S, Mizuhata Y, Inoue R, Miller GJ, Hansen SU, Jayson GC, Gardiner JM, Kanaya T, Tokitoh N, Ueda K, Takakura Y, Kioka N, Nishikawa M, Uesugi M.
  • Journal Title: J. Am. Chem. Soc. Volume: 135 Issue: 30 Pages: 11032-11039
  • DOI: 10.1021/ja4018682
  • Peer Reviewed
• [Journal Article] RNAを検出する蛍光プローブの開発 (2011)
  • Author(s): 村田亜沙子*, 佐藤慎一*, 川添嘉徳, 上杉志成
  • Journal Title: Chem. Commun. Volume: 47 Issue: 16 Pages: 4712-4714
  • DOI: 10.1039/c1cc10393h
  • Peer Reviewed
• [Journal Article] 海洋天然物オーリライドの作用機序解明 (2011)
  • Author(s): 佐藤慎一、村田亜沙子、折原翼、白川貴詩、末永聖武、木越英夫、上杉志成
  • Journal Title: Chem. Biol. Volume: 18 Issue: 1 Pages: 131-139
  • DOI: 10.1016/j.chembiol.2010.10.017
  • Peer Reviewed
• [Presentation] A Small-Molecule Based Method for Live-Cell Imaging of an Endogenous RNA (2014)
  • Author(s): Sato, S.
  • Organizer: iCeMS-RIKEN Joint Symposium on Mesoscopic Chemical Biology
  • Place of Presentation: Kyoto, Japan, Kyoto University (Symposium Organizer)
• [Presentation] A Small-Molecule Based Method for Live-Cell Imaging of an Endogenous RNA (2014)
  • Author(s): Sato S
  • Organizer: iCeMS-RIKEN Joint Symposium on Mesoscopic Chemical Biology
  • Place of Presentation: Kyoto
  • Invited
• [Presentation] 転写因子SREBPの活性化を阻害する内因性化合物 (2013)
  • Author(s): 領田優太、渡邉瑞貴、Bilon KHAMB、白川貴詩、佐藤慎一、川添嘉徳、酒井寿郎、上杉志成
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜、パシフィコ横浜
• [Presentation] 転写因子SREBPの活性化を阻害する内因性化合物 (2013)
  • Author(s): 領田優太、渡邉瑞貴、Bilon Khamb,、白川貴詩、佐藤慎一、川添嘉徳、上杉志成
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
• [Presentation] Development of small-molecule fluorescent probes for live imaging of endogenous RNAs (2012)
  • Author(s): Sato, S.
  • Place of Presentation: Fukuoka, Japan, Fukuoka International Congress Center (Workshop Organizer)
• [Presentation] Development of small-molecule fluorescent probes for live imaging of endogenous RNAs (2012)
  • Author(s): 佐藤慎一
  • Organizer: 第３５回日本分子生物学会
  • Place of Presentation: 福岡
  • Invited
• [Presentation] Marine Natural Product Aurilide Activates the OPA1-Mediated Apoptosis by Binding to Prohibitin (2012)
  • Author(s): Shin-ichi Sato, Asako Murata, Tsubasa Orihara, Takashi Shirakawa, Kiyotake Suenaga, Hideo Kigoshi, and Motonari Uesugi
  • Organizer: CLS-iCeMS Joint Symposium
  • Place of Presentation: 中国・北京
• [Presentation] 海洋天然物オーリライドの標的タンパク質決定
  • Author(s): 佐藤慎一、村田亜沙子、折原翼、白川貴詩、末永聖武、木越英夫、上杉志成
  • Organizer: 第53 回天然有機化合物討論会
  • Place of Presentation: 大阪国際交流センター(大阪府)
• [Book] Affinity-based isolation of molecular targets of clinically used drugs, Case Studies in Chemical Biology (2014)
  • Author(s): Sato, S., and Uesugi M.
• [Book] In vitro Selection of RNA Aptamers for a Small-Molecule Dye, Methods in Molecular Biology, 1111(査読有) (2014)
  • Author(s): Murata, A and Sato, S.
• [Book] Concepts and Case Studies in Chemical Biology (2014)
  • Author(s): Sato S, Uesugi M
  • Total Pages: 9
  • Publisher: Wiley-VCH Verlag
• [Book] Methods in Molecular Biology (2014)
  • Author(s): Murata A, Sato S
  • Total Pages: 13
  • Publisher: Humana Press