Role of polyol moiety of amphotericin B in ion channel formation and sterol selectivity in bilayer membrane

Tomoya Yamamoto, Yuichi Umegawa, Hiroshi Tsuchikawa, Nobuaki Matsumori, Shinya Hanashima, Michio Murata, Resul Haser, Bernard J. Rawlings, Patrick Caffrey

研究成果: Contribution to journalArticle査読

10 被引用数 (Scopus)

抄録

Amphotericin B (AmB) is a polyene macrolide antibiotic widely used to treat mycotic infections. In this paper, we focus on the role of the polyol moiety of AmB in sterol selectivity using 7-oxo-AmB, 7α-OH-AmB, and 7β-OH-AmB. The 7-OH analogs were prepared from 7-oxo-AmB. Their K+ flux activity in liposomes showed that introduction of an additional ketone or hydroxy group on the polyol moiety reduces the original activity. Conformational analyses of these derivatives indicated that intramolecular hydrogen-bonding network possibly influenced the conformational rigidity of the macrolactone ring, and stabilized the active conformation in the membrane. Additionally, the flexible polyol leads to destabilization of the whole macrolactone ring conformation, resulting in a loss of sterol selectivity.

本文言語英語
ページ(範囲)5782-5788
ページ数7
ジャーナルBioorganic and Medicinal Chemistry
23
17
DOI
出版ステータス出版済み - 4 15 2015

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子医療
  • 分子生物学
  • 薬科学
  • 創薬
  • 臨床生化学
  • 有機化学

フィンガープリント

「Role of polyol moiety of amphotericin B in ion channel formation and sterol selectivity in bilayer membrane」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル