Photoaffinity capture for the identification of functional site within proteins of nano-mol amount

• Project/Area Number: 20390032
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: University of Toyama
• Principal Investigator: HATANAKA Yasumaru University of Toyama, 大学院・医学薬学研究部, 教授 (30111181)
• Co-Investigator(Kenkyū-buntansha): TOMOHIRO Takenori 富山大学, 大学院・医学薬学研究部(薬学), 准教授 (70357581)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000); Fiscal Year 2010: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2009: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2008: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: 創薬基礎技術 / 薬物結合部位 / 質量分析 / 光アフィニティー / 光プローブ / 膜タンパク質 / 機能部位 / 構造解析 / ペルオキシソーム / β-酸化酵素 / ATP / 固相技術

Research Abstract

Recent progress in the drug developments enables the computer aided design of new medicines which are often called as "molecular target drugs." The present research developed several novel photo-activatable probes that are effective for the analysis trace amount proteins. The application of this purobe was successful for solving important binding-site within a metabolic enzyme.

Research Products

• [Journal Article] Rapidly photoactivatable ATP probes for specific labeling of tropomyosin within the actomyosin protein complex (2011)
  • Author(s): Souta Masuda, Takenori Tomohiro, Yasumaru Hatanaka
  • Journal Title: Bioorg.Med.Chem.Lett. vol.21 Pages: 2252-2254
  • Peer Reviewed
• [Journal Article] Rapidly photoactivatable ATP probes for specific labeling of tropomyosin within the actomvosin protein complex (2011)
  • Author(s): Souta Masuda, Takenori Tomohiro, Yasumaru Hatanaka
  • Journal Title: Bioorg.Med.Chem.Lett. Volume: 21(印刷中, in press (2011))
  • Peer Reviewed
• [Journal Article] Identification of a substrate-binding site in a peroxisomal β-oxidation enzyme by photoaffinity labeling with a novel palmitoyl derivative (2010)
  • Author(s): Yoshinori Kashiwayama, Takenori Tomohiro, Kotomi Narita, Miyuki Suzumura, Tuomo Glumoff, J.Kalervo Hiltunen, Paul P.Van Veldhoven, Yasumaru Hatanaka, Tsuneo Imanaka
  • Journal Title: J.Biol.Chem. vol.285 Pages: 26315-26325
  • Peer Reviewed
• [Journal Article] Efficient approach for profiling photoaffinity labeled peptides with a cleavable biotinyl photoprobe (2010)
  • Author(s): Nlandu B.Bongo, Takenori Tomohiro, Yasumaru Hatanaka
  • Journal Title: Bioorg.Med.Chem.Lett. vol.20 Pages: 1834-1836
  • Peer Reviewed
• [Journal Article] Photoactive ligands probing the sweet taste receptor. Design and synthesis of highly potent diazirinyl D-phenylalanine derivatives (2010)
  • Author(s): Katsuyoshi Masuda, Ayako Koizumi, Takumi Misaka, Yasumaru Hatanaka, Keiko Abe, Takaharu Tanaka, Masaji Ishiguro, Makoto Hashimoto
  • Journal Title: Bioorg.Med.Chem.Lett. vol.20 Pages: 1081-1083
  • NAID: 120001875431
  • Peer Reviewed
• [Journal Article] Identification of a substrate-binding site in a peroxisomal β-oxidation enzyme by photoaffinity labeling with a novel palmitoyl derivative (2010)
  • Author(s): Yoshinori Kashiwayama, Takenori Tomohiro, Kotomi Narita, Miyuki Suzumura, Tuomo Glumoff, J.Kalervo Hiltunen, Paul P.Van Veldhoven, Yasumaru Hatanaka, Tsuneo Imanaka
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 26315-26325
  • Peer Reviewed
• [Journal Article] Design and synthesis of highly potent diazirinyl D-phenylalanine derivatives (2010)
  • Author(s): Katsuyoshi Masuda
  • Journal Title: Bioorg.Med.Chem.Lett. 20 Pages: 1834-1836
  • Peer Reviewed
• [Journal Article] Efficient approach for profiling photoaffinity labeled peptides with a cleavable biotinyl photoprobe (2010)
  • Author(s): Nlandu B.Bongo
  • Journal Title: Bioorg.Med.Chem.Lett. 20 Pages: 1834-1836
  • Peer Reviewed
• [Journal Article] Synthesis and Evaluation of Novel Photoreactive α-Amino Acid Analog Carrying Acidic and Cleavable Functions (2009)
  • Author(s): Nlandu B.Bongo, Takenori Tomohiro, Yasumaru Hatanaka
  • Journal Title: Bioorg.Med.Chem.Lett. vol.19 Pages: 80-82
  • Peer Reviewed
• [Journal Article] Synthesis and Evaluation of Novel Photoreactive α-Amino Acid Analog Carrying Acidic and Cleavable Functions (2009)
  • Author(s): Nlandu B.Bongo
  • Journal Title: Bioorg.Med.Chem.Lett. 19 Pages: 80-82
  • Peer Reviewed
• [Journal Article] Recent Progress in Diazirine-Based Photoaffinity Labeling (2008)
  • Author(s): Makoto Hahimoto, Yasumaru Hatanaka
  • Journal Title: Eur.J.Org.Chem. vol.2008 Pages: 2513-2523
  • NAID: 120006390329
  • Peer Reviewed
• [Journal Article] Recent Progress in Diazirine-Based Photoaffinity Labeling(総説) (2008)
  • Author(s): Makoto Hashimoto
  • Journal Title: Eur.J.Org.Chem. 2008 Pages: 2513-2523
  • Peer Reviewed
• [Presentation] Chemical Approach for Identifying Drug Binding Site within Proteins (2010)
  • Author(s): 畑中保丸
  • Organizer: Kongres Ilmiah XVIII dan Rakernas 2010 Ikatan Apoteker Indonesia (Scientific Congress XVIII and Annual Meeting of Indonesian Pharmacist Association)
  • Place of Presentation: Makassar, Indonesia.
  • Year and Date: 2010-12-12
• [Presentation] Chemical Approach for Identifying Drug Binding Site within Proteins基調講演(招待) (2010)
  • Author(s): Yasumaru Hatanaka
  • Organizer: Kongres Ilmiah XVIII dan Rakernas 2010 Ikatan Apoteker Indonesia (Scientific Congress XVIII and Annual Meeting of Indonesian Pharmacist Association)
  • Place of Presentation: Makassar, Indonesia
  • Year and Date: 2010-12-12
• [Presentation] A Rapid and Efficient Method for Identifying Photoaffinity Labeled Sites within Proteins, Symposium for Medicinal Chemistry Division : Direct Approaches for Identifying All of the Cellular Targets of Small Molecule Drugs, and Mapping their Binding Cavities (2010)
  • Author(s): 畑中保丸
  • Organizer: the 239th National ACS Meeting
  • Place of Presentation: San Francisco, California, USA.
  • Year and Date: 2010-03-22
• [Presentation] A Rapid and Efficient Method for Identifying Photoaffinity Labeled Sites within Proteins (2010)
  • Author(s): Yasumaru Hatanaka
  • Organizer: the 239th National ACS Meeting (招待講演)
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2010-03-22
• [Presentation] Photoaffinity Labeling with Novel Cleavable Biotinyl Probe (2010)
  • Author(s): Tomohiro T., Bongo N.B., Hatanaka Y.
  • Organizer: 21st French-Japanese Symposium on Medicinal and Fine Chemistry
  • Place of Presentation: Kyoto
• [Presentation] 新規ジアジリン導入シグナルペプチドプローブの開発 (2010)
  • Author(s): 森本正大, 友廣岳則, 丸山伸之, 畑中保丸
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
• [Presentation] 発蛍光性ジアジリンとこれを導入した新規ATPプローブの開発 (2010)
  • Author(s): 猪ノ口裕二, 増田宗太, 友廣岳則, 畑中保丸
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
• [Presentation] 味覚関連アミノ酸およびペプチド用光アフィニティーラベル試薬合成 (2010)
  • Author(s): 橋本誠, 畑中保丸
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
• [Presentation] 芳香族アミノ酸側鎖構造活性相関解析用光アフィニティーラベル試薬の立体選択的合成 (2009)
  • Author(s): 橋本誠, 村重諒, 村井勇太, 畑中保丸
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
• [Presentation] 新ATP/ADPプローブによるアクトミオシン複合体の光アフィニティー解析 (2009)
  • Author(s): 増田宗太, 友廣岳則, 畑中保丸
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
• [Presentation] Bouvier M., βアドレナリン受容体に特異的なジアジリン型新規光プローブの開発 (2009)
  • Author(s): 吉田幸司, 友廣岳則, 畑中保丸, 小林弘幸
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
• [Presentation] 脂質、糖鎖、核酸等を一段階で光反応性プローブに誘導する効率的方法の開発 (2009)
  • Author(s): 谷下充佳, 友廣岳則, 畑中保丸
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
• [Presentation] βアドレナリン受容体に特異的なジアジリン型新規光プローブの開発 (2009)
  • Author(s): 吉田幸司
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
• [Presentation] Photoaffinity-Based Binding Analysis of Pt-DamagedD DNA and Nclear Protein (2008)
  • Author(s): Tomohiro, T., Sugai, A., Hatanaka, Y.
  • Organizer: the 4th Asian Biological Inorganic Chemistry Conference
  • Place of Presentation: Jeju, Korea.
• [Presentation] Photoaffinity-Based Binding Analysis of Pt-Damaged DNA and Nuclear Protein (2008)
  • Author(s): Takenori Tomohiro
  • Organizer: The 4^<th> Asian Biological Inorganic Chemistry Conference
  • Place of Presentation: Jeju, Korea
• [Remarks] ホームページ等
  • URL: http://www.pha.u-toyama.ac.jp/anachem/index-j.html
• [Remarks]
  • URL: http://www.pha.u-toyama.ac.jp/anachem/index-j.html
• [Remarks]
  • URL: http://www.pha.u-toyama.ac.jp/anachem/index-j.html
• [Remarks]
  • URL: http://www.pha.u-toyama.ac.jp/anachem/index-j.html