Development and biological application of thioamide-click type reactions

• Project/Area Number: 17K08363
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: University of Toyama
• Principal Investigator: CHIBA Junya 富山大学, 学術研究部薬学・和漢系, 准教授 (50436789)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: クリックケミストリー / 薬学 / 生体分子 / 有機化学 / チオアミド / スルホニルアジド / チオウレア

Outline of Final Research Achievements

We recently developed a new chemical reaction. In this research, we revealed that the reaction can be applied to biomolecules in water and can use as an efficient click-type reaction for in situ, target-guided synthesis of important inhibitors.

Academic Significance and Societal Importance of the Research Achievements

新しい化学反応の開発は、創薬をはじめとする「ものづくり」の可能性を飛躍的に向上させる。本研究では我々が開発した新しい化学反応に関して、特に生体系への展開を念頭に精査した。これにより、本反応を生かす方向性を特長づけることができた学術的意義は大きい。またその中でも特に、本化学反応を阻害剤候補化合物の効率的な合成に展開できた点は、社会的観点からも重要な意義を持つと考えられる。

Research Products

• [Int'l Joint Research] Hasanuddin University(インドネシア)
• [Journal Article] Additive‐Free Enzymatic Phosphorylation and Ligation of Artificial Oligonucleotides with C‐Nucleosides at the Reaction Points (2019)
  • Author(s): Oda Yutaro、Chiba Junya、Kurosaki Fumihiro、Yamade Yusuke、Inouye Masahiko
  • Journal Title: ChemBioChem Volume: 20 Issue: 15 Pages: 1945-1952
  • DOI: 10.1002/cbic.201900217
  • Peer Reviewed
• [Journal Article] Novel coupling reaction between sulfonyl azide and N,N,N',N'-tetramethylthiourea (2019)
  • Author(s): Muhammad Aswad, Junya Chiba, Yasumaru Hatanaka, Takenori Tomohiro
  • Journal Title: Tetrahedron Letters Volume: 60 Issue: 24 Pages: 1611-1613
  • DOI: 10.1016/j.tetlet.2019.05.029
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 2-Aminopyridine as a Nucleobase Substitute for Adenine in DNA-like Architectures: Synthesis of Alkynyl C-Nucleotides and Their Hybridization Characteristics (2019)
  • Author(s): Kurosaki Fumihiro、Chiba Junya、Oda Yutaro、Hino Airi、Inouye Masahiko
  • Journal Title: The Journal of Organic Chemistry Volume: 85 Issue: 4 Pages: 2666-2671
  • DOI: 10.1021/acs.joc.9b02750
  • Peer Reviewed
• [Journal Article] Simple Synthesis of Sulfonyl Amidine-Containing Glucosidase Inhibitors by a Chemoselective Coupling Reaction Between D-Gluconothiolactam and Sulfonyl Azides (2017)
  • Author(s): Aswad Muhammad、Chiba Junya、Tomohiro Takenori、Hatanaka Yasumaru
  • Journal Title: International Research Journal of Pure and Applied Chemistry Volume: 14 Issue: 2 Pages: 1-8
  • DOI: 10.9734/irjpac/2017/34259
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 完全人工アルキニル RNA の構築とその物性評価 (2020)
  • Author(s): 黒崎 史大, 千葉 順哉, 井上 将彦
  • Organizer: 日本化学会第100春季年会
• [Presentation] アジド導入ペプチドを用いた新規クリック反応の開発 (2019)
  • Author(s): 篠﨑友希，千葉順哉，友廣岳則
  • Organizer: 日本薬学会北陸支部第131回例会
• [Presentation] 脂肪酸代謝関連酵素プロファイリングを目的とした光ラベル法の開発 (2019)
  • Author(s): 萩原 智，森本正大，千葉順哉，友廣岳則
  • Organizer: 日本薬学会北陸支部第131回例会
• [Presentation] PeT-regulated tagging method for PAL-based identification of interacting protein. (2019)
  • Author(s): Takenori Tomohiro, Tsukasa Kaneko, Yusuke, Hotta, Junya Chiba, Yasumaru Hatanaka
  • Organizer: 27th French-Japanese Symposium on Medicinal&Fine Chemistry
  • Int'l Joint Research
• [Presentation] Gluconoamidinylsulfgne as a new promising anti diabetic agent: a comprehensive study based on the click-type reaction of thoamide and sulfonyl azide. (2018)
  • Author(s): M. Aswad, J. Chiba, Subehan, Habibie, S. Sukamoto, Mamada, Y. Hatanaka, T. Tomohiro
  • Organizer: The Third International Symposium on Toyama-Asia-Africa Pharmaceutical Network
  • Int'l Joint Research
• [Presentation] Improvement of target protein analysis with a photoprobe possessing N-acylsulfonamide as a cleavable linkage. (2018)
  • Author(s): R. Hayashi, S. Morimoto, J. Chiba, Y. Hatanaka, T. Tomohiro
  • Organizer: The Third International Symposium on Toyama-Asia-Africa Pharmaceutical Network
  • Int'l Joint Research
• [Presentation] アシルスルホンアミド型光反応基による標的タンパク質解析の効率化 (2018)
  • Author(s): 林 龍二、森本 正大、千葉 順哉、畑中 保丸、友廣 岳則
  • Organizer: 日本薬学会北陸支部第１３０回例会
• [Presentation] Distance Dependence of the Electron-Transfer Rate of Electrode-Bound Duplex DNAs Modified with a Distal Redox Unit (2018)
  • Author(s): Junya Chiba, Shun Aoki, Masahiko Inouye
  • Organizer: The 6th International Symposium "Dynamical ordering of biomolecular systems for creation of integrated functions"
  • Int'l Joint Research
• [Presentation] スルホクリック反応を利用した光反応性プローブの簡便合成と標的タンパク質同定の効率化 (2017)
  • Author(s): 林 龍二, 森本 正大, 千葉 順哉, 畑中 保丸, 友廣 岳則
  • Organizer: 日本プロテオーム学会 2017年大会
• [Presentation] PAL-based fluorogenic tagging for structural analysis of ligand binding state within target protein (2017)
  • Author(s): Takenori Tomohiro, Reona Yamaguchi, Shota Morimoto, Junya Chiba, Yasumaru Hatanaka
  • Organizer: 26th French-Japanese Symposium on Medicinal&Fine Chemistry
  • Int'l Joint Research
• [Remarks] 富山大学薬学部 薬化学研究室
  • URL: http://www.pha.u-toyama.ac.jp/yakka/index-j.html
• [Remarks] 富山大学薬学部 生体認識化学研究室
  • URL: http://www.pha.u-toyama.ac.jp/anachem/anachem/homu.html
• [Patent(Industrial Property Rights)] 人工核酸 (2020)
  • Inventor(s): 千葉順哉, 井上将彦, 黒崎史大
  • Industrial Property Rights Holder: 国立大学法人富山大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2020-036320
  • Filing Date: 2020
• [Patent(Industrial Property Rights)] スルホニルアジド安息香酸誘導体およびその反応性誘導体 (2017)
  • Inventor(s): 千葉順哉、友廣岳則、畑中保丸
  • Industrial Property Rights Holder: 千葉順哉、友廣岳則、畑中保丸
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2017-146208
  • Filing Date: 2017