AGE-RAGE interaction as a target for drug design against diabetes complications

• Project/Area Number: 20790034
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Physical pharmacy
• Research Institution: Osaka University
• Principal Investigator: YOSHIDA Takuya Osaka University, 薬学研究科, 助教 (00294116)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 構造生物学 / AGE / RAGE / 立体構造 / 創薬

Research Abstract

We have analyzed the conformational dynamics of the variable-type domain of RAGE (Receptor for AGE), which has been revealed to contain the binding site of AGE. Based on the results of NMR and MD calculation, a combination of virtual and in vitro screening was carried out to find suitable chemical compounds to interfere with the AGE-RAGE binding. As a result, chemical compounds were identified as candidates for RAGE inhibitor.

Research Products

• [Journal Article] Structure and reaction mechanism of human nicotinamide phosphoribosyltransferase (2010)
  • Author(s): Takahashi R, Nakamura S, Nakazawa T, Minoura K, Yoshida T, Nishi Y, Kobayashi Y, Ohkubo T.
  • Journal Title: J Biochem. 147 Pages: 95-107
  • NAID: 10027873352
  • Peer Reviewed
• [Journal Article] Structure and reaction mechanism of human nicotinamide phosphoribosyltransferase. (2010)
  • Author(s): Takahashi R., et al.
  • Journal Title: J.Biochem. 147 Pages: 95-107
  • Peer Reviewed
• [Journal Article] Solution structure of the variable-type domain of the receptor for advanced glycation end products: new insight into AGE-RAGE interaction. (2008)
  • Author(s): Matsumoto S, Yoshida T, Murata H, Harada S, Fujita N, Nakamura S, Yamamoto Y, Watanabe T, Yonekura H, Yamamoto H, Ohkubo T, Kobayashi Y.
  • Journal Title: Biochemistry 47 Pages: 12299-311
  • Peer Reviewed
• [Journal Article] Solution Structure of the Variable-Type Domain of the Receptor for Advanced Glycation End Products : New Insight into AGE-RAGE Interaction (2008)
  • Author(s): Matsumoto, S., et.al.
  • Journal Title: Biochemistry 47 Pages: 12299-12311
  • Peer Reviewed
• [Presentation] 立体構造に基づく終末糖化産物AGE受容体とリガンド間の相互作用解析 (2010)
  • Author(s): 藤田直子, 吉田卓也, 他
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山市
  • Year and Date: 2010-03-29
• [Presentation] 立体構造に基づく終末糖化産物AGE受容体とリガンド間の相互作用解析 (2010)
  • Author(s): 藤田直子
  • Organizer: 日本薬学会 年会
  • Place of Presentation: 岡山大学(岡山県)
  • Year and Date: 2010-03-29
• [Presentation] 非線形サンプリングデータ解析法の改良 (2009)
  • Author(s): 吉田卓也, 他
  • Organizer: NMR討論会
  • Place of Presentation: 福岡市
  • Year and Date: 2009-11-11
• [Presentation] 非線形サンプリングデータ解析法の改良 (2009)
  • Author(s): 吉田卓也
  • Organizer: NMR討論会
  • Place of Presentation: 九州大学(福岡県)
  • Year and Date: 2009-11-11
• [Presentation] AGEレセプター阻害化合物の探索と評価 (2008)
  • Author(s): 原田秀作, 吉田卓也, 他
  • Organizer: 第55回日本生化学会近畿支部例会
  • Place of Presentation: 大阪市
  • Year and Date: 2008-05-24
• [Presentation] AGEレセプター阻害化合物の探索と評価 (2008)
  • Author(s): 原田秀作
  • Organizer: 第55回日本生化学会近畿支部例会
  • Place of Presentation: 大阪市住吉区
  • Year and Date: 2008-05-24