Structure-based design of a bioactive small molecule

• Project/Area Number: 21870016
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Structural biochemistry
• Research Institution: Kyoto University
• Principal Investigator: SATO Shinichi Kyoto University, 物質ー細胞統合システム拠点, 助教 (70534478)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥2,704,000 (Direct Cost: ¥2,080,000、Indirect Cost: ¥624,000); Fiscal Year 2010: ¥1,287,000 (Direct Cost: ¥990,000、Indirect Cost: ¥297,000); Fiscal Year 2009: ¥1,417,000 (Direct Cost: ¥1,090,000、Indirect Cost: ¥327,000)
• Keywords: X線結晶解析 / 標的タンパク質同定 / 生理活性化合物 / 分子設計 / 分子認識

Research Abstract

The goal of this project is to solve the X-ray structure of wrenchnolol-target-protein complex and to obtain a wrenchnolol analogue which has a good potency by structure-based design.
: Research results :
1. Three kinds of S100 protein (S100A11, A13 and A16), which are purified as protein targets of wrenchnolol, were prepared by using E. coli expression system.
2. 1g of wrenchnolol was prepared by chemical synthesis.
3. The S100 protein-wrenchnolol complex was formed by mixing and incubating on ice for 30min, and then concentrated by ultrafiltration.
4. The initial crystallization conditions for the complex were screened by using crystal screening kits. In this screening, several protein crystals were obtained.

Research Products

• [Journal Article] Small-molecule fluorescent probes for specific RNA targets Chem. (2011)
  • Author(s): Murata, A., Sato, S., Kawazoe, Y., Uesugi M.
  • Journal Title: Comm. 47(16) Pages: 4712-4714
  • Peer Reviewed
• [Journal Article] Marine Natural Product Aurilide Activates the OPA1-Mediated Apoptosis by Binding to Prohibitin Chem. (2011)
  • Author(s): Sato, S., Murata, A., Orihara, T.,Shirakawa, T., Suenaga, K., Kigoshi, H., Uesugi, M.
  • Journal Title: Biol. 18(1) Pages: 131-139
  • Peer Reviewed
• [Journal Article] Deactivation of STAT6 through serine 707 phosphorylation by JNK (2011)
  • Author(s): Shirakawa, T., Kawazoe, Y., Tsujikawa, T., Jung, D., Sato, S., Uesugi M.
  • Journal Title: J.Biol.Chem. 286(5) Pages: 4003-4010
  • Peer Reviewed
• [Journal Article] Small-molecule fluorescent probes for specific RNA targets (2011)
  • Author(s): Murata, A., Sato, S., Kawazoe, Y., Uesugi M.
  • Journal Title: Chemical Communications Volume: 47 Pages: 4712-4714
  • Peer Reviewed
• [Journal Article] Marine Natural Product Aurilide Activates the OPA1-Mediated Apoptosis by Binding to Prohibitin (2011)
  • Author(s): Sato, S., Murata, A., Orihara, T., Shirakawa, T., Suenaga, K., Kigoshi, H., Uesugi, M.
  • Journal Title: Chemistry & Biology Volume: 18 Pages: 131-139
  • NAID: 120002807468
  • Peer Reviewed
• [Journal Article] Deactivation of STAT6 through serine 707 phosphorylation by JNK (2011)
  • Author(s): Shirakawa, T., Kawazoe, Y., Tsujikawa, T., Jung, D., Sato, S., Uesugi M.
  • Journal Title: The Journal of Biological Chemistry Volume: 286 Pages: 4003-4010
  • Peer Reviewed
• [Journal Article] Biochemical target isolation for novices : affinity-based strategies Chem. (2010)
  • Author(s): Sato, S., Murata, A., Shirakawa, T.,Uesugi, M.
  • Journal Title: Biol. 17(6) Pages: 616-623
  • Peer Reviewed
• [Journal Article] Biochemical target isolation for novices : affinity-based strategies (2010)
  • Author(s): Sato, S., Murata, A., Shirakawa, T., Uesugi, M.
  • Journal Title: Chemistry & Biology Volume: 17 Pages: 616-623
  • Peer Reviewed
• [Journal Article] 化合物推理ゲーム (2010)
  • Author(s): Sato, S., Uesugi, M.
  • Journal Title: ファルマシア 46(1) Pages: 83-86
• [Journal Article] 海洋天然物のケミカルジェネティクス (2009)
  • Author(s): Sato, S., Murata, A., Uesugi, M.
  • Journal Title: 細胞工学 28(4) Pages: 332-337
• [Journal Article] 化合物推理ゲーム (2009)
  • Author(s): Sato, S., Uesugi, M.
  • Journal Title: ファルマシア 45(12) Pages: 1263-1266
• [Presentation] Marine Natural Product Aurilide Activates the OPA1-Mediated Apoptosis by Binding to Prohibitin. (2010)
  • Author(s): Sato, S., Murata, A., Orihara, T.,Suenaga, K., Kigoshi, H., Uesugi, M.
  • Organizer: The 8th iCeMS International Symposium : “Meso-Control of Functional Architecture"
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-11-09
• [Presentation] Natural Product Aurilide Activates the OPA1-Mediated Apoptosis by Binding to Prohibitin. (2010)
  • Author(s): Sato, S., Murata, A., Orihara, T., Suenaga, K., Kigoshi, H., Uesugi, M.
  • Organizer: The 8th iCeMS International Symposium
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-11-01
• [Presentation] Protein Target Identification of Bioactive Small Molecules. (2010)
  • Author(s): Sato S.
  • Organizer: Department of Chemistry Seminar
  • Place of Presentation: Athens, Georgia, USA, University of Georgia (招待講演)
  • Year and Date: 2010-10-06
• [Presentation] Protein Target Identification of Bioactive Small Molecules. (2010)
  • Author(s): Sato, S.
  • Organizer: University of Georgia, Department of Chemistry Seminar
  • Place of Presentation: Athens, Georgia, USA
  • Year and Date: 2010-10-06
• [Presentation] Small molecule-based FRET probes for specific RNA targets. (2010)
  • Author(s): Murata, A., Sato, S., Kawazoe, Y., Uesugi M.
  • Organizer: The 5th Japan-Korea Chemical Biology Symposium
  • Place of Presentation: Busan, Korea
  • Year and Date: 2010-01-26
• [Presentation] Marine Natural Product Aurilide Activates the OPA1-Mediated Apoptosis by Binding to Prohibitin. (2009)
  • Author(s): Sato, S., Murata, A., Orihara, T., Suenaga, K., Kigoshi, H., Uesugi, M.
  • Organizer: The 25th Naito Conference on Chemical Biology [II]
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 2009-09-10
• [Presentation] The Marine Natural Product, Aurilide, Activates OPAl-mediated Apoptosis by Targeting Prohibitin (2009)
  • Author(s): 佐藤慎一
  • Organizer: 第25回内藤コンファレンス
  • Place of Presentation: 北海道・札幌
  • Year and Date: 2009-09-10
• [Book] 生理活性物質による創薬標的同定のコツ(創薬研究のためのタンパク質・プロテオミクス解析) 別冊 (2010)
  • Author(s): 佐藤慎一, 村田亜沙子, 白川貴詩, 上杉志成
  • Publisher: 羊土社出版
• [Book] ファルマシア(化合物推理ゲーム) 46(1) (2010)
  • Author(s): 佐藤慎一, 上杉志成
• [Book] 生理活性物質による創薬標的同定のコツ (2010)
  • Author(s): 佐藤慎一, 村田亜沙子, 白川貴詩, 上杉志成
  • Total Pages: 5
  • Publisher: 創薬研究のためのタンパク質・プロテオミクス解析
• [Book] 細胞工学(海洋天然物のケミカルジェネティクス) 28 (2009)
  • Author(s): 佐藤慎一, 村田亜沙子, 上杉志成
  • Publisher: 学研メディカル秀潤社出版
• [Book] ファルマシア(化合物推理ゲーム) 45(12) (2009)
  • Author(s): 佐藤慎一,上杉志成