Rational design of protein-protein interaction inhibitors

2013 Fiscal Year Final Research Report

• 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
• 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
  • Peer Reviewed
• [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
• [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)
  • Year and Date: 20140200
• [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
  • Year and Date: 20130000
• [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)
  • Year and Date: 20121200
• [Book] Affinity-based isolation of molecular targets of clinically used drugs, Case Studies in Chemical Biology (2014)
  • Author(s): Sato, S., and Uesugi M.
  • Total Pages: in press
• [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.
  • Total Pages: 17-28