Development of a novel type of irreversible inhibitors for comprehensive analysis of protein phosphatase in cells

• Project/Area Number: 19710195
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Living organism molecular science
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: HIRAI Go The Institute of Physical and Chemical Research, 袖岡有機合成化学研究室, 研究員 (50359551)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,490,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: プロテインホスファターゼ / 有機合成 / 不可逆的阻害剤 / 蛍光ラベル体 / 分子プローブ

Research Abstract

細胞内のタンパク質脱リン酸化酵素(プロテインホスファターゼ)の機能を停止させる新しいタイプの阻害剤を創製した。この阻害剤はプロテインホスファターゼと共有結合で連結する不可逆的阻害剤として設計し、実際にがん細胞の細胞周期を調節するホスファターゼCdc25Aと共有結合を形成することを見出した。また細胞内でこの阻害剤が相互作用するタンパク質を、蛍光ラベル体を用いて検出することに成功した。

Research Products

• [Journal Article] Limited Inhibitory Effects of Oseltamivir and Zanamivir on Human Sialidases (2008)
  • Author(s): Keiko Hata, Koichi Koseki, Kazunori Yamaguchi, Setsuko Moriya, Yasuo Suzuki, Sangchai Yingsakmongkon, Go Hirai, Mikiko Sodeoka, Mark von Itzstein, Taeko Miyagi
  • Journal Title: Antimicrob. Agents Chemother 52 Pages: 3484-3491
  • Peer Reviewed
• [Journal Article] Synthesis of CH_2-Linked・(2,3)Sialylgalactose Analogue : On the Stereoselectivity of the Key Ireland-Claisen Rearrangement (2008)
  • Author(s): Toru Watanabe, Go Hirai, Marie Kato, Daisuke Hashizume, Taeko Miyagi, Mikiko Sodeoka
  • Journal Title: Org. Lett. 10 Pages: 4167-4170
  • Peer Reviewed
• [Journal Article] Synthesis of CH2-Linked α(2,3)Sialylgalactose Analogue: On the Stereoselectivity of the Key Ireland-Claisen Rearrangement (2008)
  • Author(s): Toru Watanabe
  • Journal Title: Org. Lett. 10 Pages: 4167-4170
  • Peer Reviewed
• [Journal Article] Limited Inhibitory Effects of Oseltamivir and Zanamivir on Human Sialidases (2008)
  • Author(s): Keiko Hata
  • Journal Title: Antimicrob. Agents Chemother 52 Pages: 3484-3491
  • Peer Reviewed
• [Journal Article] Stereocontrolled and Convergent Entry to CF_2-Sialosides : Synthesis of CF_2-Linked Ganglioside GM4 (2007)
  • Author(s): Go Hirai, Toru Watanabe, Kazunori Yamaguchi, Taeko Miyagi, Mikiko Sodeoka
  • Journal Title: J. Am. Chem. Soc. 129 Pages: 15420-15421
  • Peer Reviewed
• [Journal Article] Importance of interaction between C1 domain and lipids in protein kinase Ca activation : Hydrophobic side chain direction in isobensofuranone ligands controls enzyme activation level (2007)
  • Author(s): Go Hirai, Tadashi Shimizu, Toru Watanabe, Yosuke Ogoshi, Megumi Ohkubo, Mikiko Sodeoka
  • Journal Title: ChemMedChem 2 Pages: 1006-1009
  • Peer Reviewed
• [Journal Article] Importance of interaction between C1 domain and lipids in protein kinase Cα activation: Hydrophobic side chain direction in isobenzofuranone ligands controls enzyme activation level. (2007)
  • Author(s): Go Hirai
  • Journal Title: Chem Med Chem 2 Pages: 1006-1009
  • Peer Reviewed
• [Journal Article] Stereocontrolled and Convergent Entry to CF_2-Sialosides: Synthesis of CF_2-Linked Ganglioside GM4 (2007)
  • Author(s): Go Hirai
  • Journal Title: Journal of the American Chemical Society 129 Pages: 15420-15421
  • Peer Reviewed
• [Presentation] ホスファターゼの網羅的解析法を志向した分子プローブの創製と評価 (2009)
  • Author(s): 土屋綾子
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
  • Year and Date: 2009-03-27
• [Presentation] ホスファターゼの網羅的解析法を志向した分子プローブの創製と評価 (2009)
  • Author(s): 土屋綾子
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都大学
• [Presentation] Development of RK-682 enamide derivatives and attempts at comprehensive analysis of their target proteins in cells (2008)
  • Author(s): Go Hirai
  • Organizer: THE 22nd NAITO CONFERENCE ON Chemical Biology[I]
  • Place of Presentation: Sapporo
  • Year and Date: 2008-09-11
• [Presentation] RK-682エナミド誘導体標的酵素の網羅的解析法の開発 (2008)
  • Author(s): 平井 剛
  • Organizer: 日本化学会第88春季年会
  • Place of Presentation: 立教大学
  • Year and Date: 2008-03-29
• [Presentation] RE誘導体をプローブとしたホスファターゼ網羅的解析法の開発 (2008)
  • Author(s): 土屋綾子
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
• [Presentation] RK-682エナミド誘導体標的酵素の網羅的解析法の開発 (2008)
  • Author(s): 平井剛
  • Organizer: 日本化学会第88春季年会
  • Place of Presentation: 東京
• [Presentation] RK-682エナミド誘導体標的酵素の網羅的解析法の開発 (2008)
  • Author(s): 平井剛
  • Organizer: 日本ケミカルバイオロジー研究会第三回年会
  • Place of Presentation: 東京
• [Presentation] Development of RK-682 enamide derivatives and attempts at comprehensive analysis of their target proteins in cells (2008)
  • Author(s): Go Hirai
  • Organizer: THE 22nd NAITO CONFERENCE ON Chemical Biology [I]
  • Place of Presentation: 札幌
• [Presentation] Development of Dual-specificity Protein Phosphatase Inhibitor (2008)
  • Author(s): Go Hirai
  • Organizer: The First RIKEN Chemical Biolgy Deprtmnt Internatioal Symposium
  • Place of Presentation: 熱海
• [Presentation] 細胞内ホスファターゼ解析を志向した不可逆的阻害剤の開発 (2007)
  • Author(s): 平井剛
  • Organizer: 平成19年度「若手研究者のためのセミナー」
  • Place of Presentation: 慶応大学
  • Year and Date: 2007-10-27