A synthetic approach to the channel complex structure of antibiotic in a membrane: Backbone 19F-labeled amphotericin B for solidstate NMR analysis

Hiroshi Tsuchikawa, Yuichi Umegawa, Michio Murata, Tohru Oishi

Research output: Contribution to journalArticle

Abstract

Over 40 years have passed since a well-known hypothesis of a channel-like amphotericin B (AmB) assembly with ergosterol (Erg) was proposed as the mode of action accounting for its selective fungal toxicity. However, no reliable or direct experimental evidence had been obtained until recently mainly because of significant difficulties in structural analysis of the self-assembly of small molecules specifically formed inside a membrane. In this study, we describe the accomplishments in the chemical synthesis of two AmB derivatives with fluorine labeling in the molecular skeleton for applying solid-state NMR techniques. The interatomic distance measurements using these chemically prepared probes have successfully shown the detailed AmB-Erg bimolecular interaction in the channel structure for the first time. The latest solid-state NMR analysis backed by synthetic chemistry is expected to achieve a breakthrough in elucidating the long-unsolved AmB channel architecture.

Original languageEnglish
Pages (from-to)1197-1205
Number of pages9
JournalYuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
Volume76
Issue number11
DOIs
Publication statusPublished - 2018

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

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