Development of Protein-Protein Interaction Inhibitors

• Project/Area Number: 25670050
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Drug development chemistry
• Research Institution: Hokkaido University
• Principal Investigator: ICHIKAWA SATOSHI 北海道大学, 薬学研究科(研究院), 准教授 (60333621)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: タンパク質タンパク質間相互作用 / 薬物設計 / 有機合成 / 蛋白質間相互作用 / 化合物ライブラリー / 多成分反応 / 創薬化学

Outline of Final Research Achievements

It is a quite important issue to develop a strategy for rational design of protein-protein interaction inhibitors (PPIs). In this study, a small library of PPIs with diverse structures was first designed and synthesized. We have found that several compounds inhibit a protein-protein interaction with a moderate activity. A larger set of library was further synthesized.

Research Products

• [Journal Article] Expansion of Antibacterial Spectrum of Muraymycins toward Pseudomonas aeruginosa. (2014)
  • Author(s): Takeoka, Yusuke; Tanino, Tetsuya; Sekiguchi, Mitsuaki; Yonezawa, Shuji; Sakagami, Masahiro; Takahashi, Fumiyo; Togame, Hiroko; Tanaka, Yoshikazu; Takemoto, Hiroshi; Ichikawa, Satoshi*; Matsuda. Akira.
  • Journal Title: ACS Med. Chem. Lett. Volume: 5 Issue: 5 Pages: 556-560
  • DOI: 10.1021/ml5000096
  • Peer Reviewed
• [Journal Article] Synthesis and Biological Evaluation of Quinaldopeptin. (2014)
  • Author(s): Katayama, Katsushi; Okamura, Takuya; Sunadome, Takuya; Nakagawa, Koji; Takeda, Hiroshi; Shiro, Motoo; Matsuda, Akira; Ichikawa, Satoshi
  • Journal Title: J. Org. Chem. Volume: 79 Issue: 6 Pages: 2580-2590
  • DOI: 10.1021/jo500039d
  • Peer Reviewed
• [Journal Article] Function-oriented Synthesis of Liponucleoside Natural Products. (2014)
  • Author(s): Tanino, Tetsuya; Yamaguchi, Mayumi; Matsuda, Akira; Ichikawa, Satoshi
  • Journal Title: Eur. J. Org. Chem. Volume: 9 Issue: 9 Pages: 1836-1840
  • DOI: 10.1002/ejoc.201400140
  • Peer Reviewed
• [Journal Article] Total Synthesis of Quinaldopeptin and Its Analogues. (2013)
  • Author(s): Ichikawa, Satoshi*; Takuya Okamura, and Matsuda, Akira.
  • Journal Title: J. Org. Chem. Volume: 78 Issue: 24 Pages: 12662-12670
  • DOI: 10.1021/jo402267r
  • Peer Reviewed
• [Journal Article] Total Synthesis of Sandramycin and Its Analogues via a Multi-component Assemblage. (2013)
  • Author(s): Katayama, Katsushi; Nakagawa, Koji; Takeda, Hiroshi; Matsuda, Akira; Ichikawa, Satoshi
  • Journal Title: Org. Lett. Volume: 16 Issue: 2 Pages: 428-431
  • DOI: 10.1021/ol403319m
  • Peer Reviewed
• [Journal Article] Synthesis of C-Glycosyl Pyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones as a Scaffold for Check Point 1 Kinase Inhibitors. (2013)
  • Author(s): Ichikawa, Satoshi*; Tatebayashi, Nana and Matsuda, Akira.
  • Journal Title: J. Org. Chem. Volume: 78 Issue: 23 Pages: 12065-12075
  • DOI: 10.1021/jo4020672
  • Peer Reviewed
• [Presentation] ラクタム縮環型イソキサゾリジン誘導体の合成研究 (2014)
  • Author(s): 山田 早、松田 彰、市川 聡
  • Organizer: 第44回複素環化学討論会
  • Place of Presentation: 札幌
  • Year and Date: 2014-09-10 – 2014-09-12
• [Presentation] ヌクレオシド系天然物による創薬基盤研究 (2014)
  • Author(s): 市川 聡
  • Organizer: 日本薬学会134年会シンポジウム
  • Place of Presentation: 熊本大学（熊本）
  • Invited
• [Presentation] シリンゴリンAを基盤とした新規プロテアソーム阻害剤の創製研究 (2014)
  • Author(s): 千葉拓也、松田彰、市川聡
  • Organizer: 日本薬学会 第134年会
  • Place of Presentation: 熊本大学（熊本）
• [Presentation] aza-Prins反応を用いた新規カプラザマイシン誘導体の合成研究 (2014)
  • Author(s): 仲谷岳志、松田彰、市川聡
  • Organizer: 日本薬学会 第134年会
  • Place of Presentation: 熊本大学（熊本）
• [Presentation] ジアステレオ選択的Ugi三成分反応による3-ヒドロキシプロリンの合成とPlusbacin A3の全合成への応用 (2014)
  • Author(s): 勝山彬、松田彰、市川聡
  • Organizer: 日本薬学会 第134年会
  • Place of Presentation: 熊本大学（熊本）
• [Presentation] Quinaldopeptin誘導体の合成 (2014)
  • Author(s): 藤沼雅巳、松田彰、市川聡
  • Organizer: 日本薬学会 第134年会
  • Place of Presentation: 熊本大学（熊本）
• [Presentation] シリンゴリンAの全合成とその構造活性相関研究 (2013)
  • Author(s): 千葉拓也、松田彰、市川聡
  • Organizer: 第十一回 次世代を担う有機化学シンポジウム
  • Place of Presentation: 日本薬学会長井記念ホール（東京）
• [Presentation] Total Synthesis of Syringolin A, a Potent Proteasome Inhibitor (2013)
  • Author(s): 千葉拓也、松田彰、市川聡
  • Organizer: 13th International Conference on the Chemistry of Antibiotics and other bioactive compounds
  • Place of Presentation: 富士ビューホテル（山梨）
• [Presentation] Synthesis and propaties of functionalized dumbbell oligodeoxynucleotides by Cu(I) catalyzed alkyne-azide cycloaddition (2013)
  • Author(s): 砂留拓矢、市川聡、松田彰
  • Organizer: The 40th International Symposium on Nucleic Acids Chemistry 2013
  • Place of Presentation: 神奈川大学（横浜）
• [Presentation] ムレイドマイシンA誘導体の合成研究 (2013)
  • Author(s): 中村公佑、松田彰、市川聡
  • Organizer: 日本薬学会 北海道支部第140回例会
  • Place of Presentation: 札幌コンベンションセンター（北海道）
• [Presentation] ムレイドマイシンA誘導体の合成研究 (2013)
  • Author(s): 中村公佑、松田彰、市川聡
  • Organizer: 第55回 天然有機化合物討論会
  • Place of Presentation: 同志社大学寒梅館（京都）