Synthesis of 6-F-ergosterol and its influence on membrane-permeabilization of amphotericin B and amphidinol 3

Yusuke Kasai, Nobuaki Matsumori, Hiroyuki Ueno, Kenichi Nonomura, Shinya Yano, Murata Michio, Tohru Oishi

研究成果: ジャーナルへの寄稿記事

5 引用 (Scopus)

抄録

Two well-known antifungals, amphotericin B (AmB) and amphodinol 3 (AM3), are thought to exert antifungal activity by forming ion-permeable channels or pores together with sterol molecules. However, detailed molecular recognitions for AmB-sterol and AM3-sterol in lipid bilayers have yet to be determined. Toward 19F NMR-based investigation of the molecular recognition underlying their potent antifungal activity, we synthesized 6-fluoro-ergosterol in five steps via ring opening of (5α,6α)-epoxide of ergosterol acetate with using novel combination of TiF4 and n-Bu 4N+Ph3SiF2-. Then we evaluated its activity of promoting pore formation of AmB and AM3, and found that pore formation of AmB was barely promoted by 6-F-ergosterol in clear contrast to the dramatic promotion effect of unmodified ergosterol, whereas AM3 activity was markedly enhanced in the presence of 6-F-ergosterol, which was comparable to that of unmodified ergosterol. These results indicate that the introduction of an F atom at C6 position of ergosterol plays an inhibitory role in interacting with AmB, but it is not the case with AM3.

元の言語英語
ページ(範囲)1437-1442
ページ数6
ジャーナルOrganic and Biomolecular Chemistry
9
発行部数5
DOI
出版物ステータス出版済み - 3 1 2011

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Amphotericin B
Ergosterol
membranes
Membranes
Sterols
synthesis
Molecular recognition
porosity
epoxy compounds
promotion
Lipid bilayers
Epoxy Compounds
lipids
Lipid Bilayers
acetates
Ion Channels
Acetates
nuclear magnetic resonance
Nuclear magnetic resonance
6-fluoroergosterol

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

これを引用

Synthesis of 6-F-ergosterol and its influence on membrane-permeabilization of amphotericin B and amphidinol 3. / Kasai, Yusuke; Matsumori, Nobuaki; Ueno, Hiroyuki; Nonomura, Kenichi; Yano, Shinya; Michio, Murata; Oishi, Tohru.

:: Organic and Biomolecular Chemistry, 巻 9, 番号 5, 01.03.2011, p. 1437-1442.

研究成果: ジャーナルへの寄稿記事

Kasai, Yusuke ; Matsumori, Nobuaki ; Ueno, Hiroyuki ; Nonomura, Kenichi ; Yano, Shinya ; Michio, Murata ; Oishi, Tohru. / Synthesis of 6-F-ergosterol and its influence on membrane-permeabilization of amphotericin B and amphidinol 3. :: Organic and Biomolecular Chemistry. 2011 ; 巻 9, 番号 5. pp. 1437-1442.
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