Structral analysis of amphotericin B channel complex using solid-state NMR

• Project/Area Number: 25750383
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biomolecular chemistry
• Research Institution: Osaka University
• Principal Investigator: UMEGAWA Yuichi 大阪大学, 理学(系)研究科(研究院), 助教 (20587779)
• Research Collaborator: MURATA Michio 大阪大学, 理学研究科, 教授 (40183652) ; MATSUMORI Nobuaki 九州大学, 理学研究院, 教授 (50314357)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: アンフォテリシンB / リン脂質二重膜 / 固体NMR

Outline of Final Research Achievements

Sterol derivatives which have different side-chain or alicyclic structures were synthesized, and their affinities to amphotericin B (AmB) were evaluated by using ion-flux assay. The results indicated that face-face Van der Waals interactions stabilized the AmB-ergosterol complex. Solid-state NMR using fluorine 19 or carbon 13 labeled AmB and/or ergosterol were examined to obtain intermolecular distance information.

Research Products

• [Journal Article] Axial Hydrogen at C7 Position and Bumpy Tetracyclic Core Markedly Reduce Sterol’s Affinity to Amphotericin B in Membrane (2015)
  • Author(s): Nakagawa, Y., Umegawa, Y., Nonomura, K., Matsushita, N., Takano, T., Tsuchikawa, H., Hanashima, S., Oishi, T., Matsumori, N., and Murata, M.
  • Journal Title: Biochemistry Volume: 54 Issue: 2 Pages: 303-312
  • DOI: 10.1021/bi5012942
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effect of sterol side chain on ion channel formation by amphotericin B in lipid bilayers. (2014)
  • Author(s): Nakagawa, Y., Umegawa, Y., Takano, T., Tsuchikawa, H., Matsumori, N., and Murata, M.
  • Journal Title: Biochemistry Volume: 53 Issue: 19 Pages: 3088-3094
  • DOI: 10.1021/bi500122c
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] ポリオール部分の相互作用解析を目指した新規アンフォテリシンB誘導体の調製とイオンチャネル活性 (2015)
  • Author(s): 山本智也、梅川雄一、土川博史、花島慎弥、村田道雄、松森信明、Patrick Caffrey
  • Organizer: 日本化学会 第95春季年会
  • Place of Presentation: 日本大学
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] New synthetic route for labelled Amphotericin B derivative via β glycosidation (2014)
  • Author(s): Tomoya Yamamoto, Yuichi Uegawa, Hiroshi Tsuchikawa, Shinya Hanashima, Nobuaki Matsumori, Michio Murata
  • Organizer: The 3rd International Symposium on Chemical Biology of Natural Products: Target ID and Regulation of Bioactivity
  • Place of Presentation: 千里ライフサイエンスセンター
  • Year and Date: 2014-10-28 – 2014-10-29
• [Presentation] Synthesis of deuterated Amphotericin B derivative via beta-glycosidation (2014)
  • Author(s): Tomoya Yamamoto, Yuichi Umegawa, Hiroshi Tsuchikawa, Shinya Hanashima, Nobuaki Matsumori, Michio Murata
  • Organizer: Gordon Research Conference: Natural Product
  • Place of Presentation: Andover, NH, USA
  • Year and Date: 2014-07-20 – 2014-07-25
• [Presentation] Interactions of synthetic ergosterol analogues with amphotericin B toward understanding drug’s selective toxicity (2014)
  • Author(s): Yasuo Nakagawa, Yuichi Umegawa, Kenichi Nonomura, Hiroshi Tsuchikawa, Nobuaki Matsumori, Michio Murata
  • Organizer: 15th Tetrahedron symposium
  • Place of Presentation: London, UK
  • Year and Date: 2014-06-25 – 2014-06-27
• [Presentation] 新規重水素化アンフォテリシンB誘導体の合成と固体NMRによる配向解析
  • Author(s): 山本智也、梅川雄一、土川博史、花島慎弥、松森信明、村田道雄
  • Organizer: 日本化学会第94春季年会
  • Place of Presentation: 名古屋大学
• [Presentation] 分子間距離情報に基づく脂質二重膜に形成されるアンフォテリシンB複合体の構造解析
  • Author(s): 中川泰男、野々村健一、梅川雄一、・土川博史、松森信明、村田道雄
  • Organizer: 日本化学会第94春季年会
  • Place of Presentation: 名古屋大学
• [Presentation] 固体NMRによる脂質二重膜中での複合体構造解析
  • Author(s): 梅川雄一
  • Organizer: 「天然物ケミカルバイオロジー」第3回若手研究者ワークショップ
  • Place of Presentation: 東京
  • Invited
• [Presentation] Solid-state NMR based analysis of interaction between amphotericin B and ergosterol in lipid bilayer
  • Author(s): Yasuo Nakagawa, Yuichi Umegawa, Hiroshi Tsuchikawa, Nobuaki Matsumori, Michio Murata
  • Organizer: 14th Tetrahedron symposium Asia edition
  • Place of Presentation: Soul, Korea
• [Presentation] Solid-state NMR-based structure elucidation of ion channel assembly formed by amphotericin B in lipid bilayers
  • Author(s): Yasuo Nakagawa, Yuichi Umegawa, Hiroshi Tsuchikawa, Nobuaki Matsumori, Michio Murata
  • Organizer: 3rd Junior International Conference on Cutting-Edge Organic Chemistry in Asia
  • Place of Presentation: 千葉