Journal of Synthetic Organic Chemistry, Japan
Online ISSN : 1883-6526
Print ISSN : 0037-9980
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A Synthetic Approach to the Channel Complex Structure of Antibiotic in a Membrane: Backbone 19F-Labeled Amphotericin B for Solid-State NMR Analysis
Hiroshi TsuchikawaYuichi UmegawaMichio MurataTohru Oishi
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2018 Volume 76 Issue 11 Pages 1197-1205

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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.

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© 2018 The Society of Synthetic Organic Chemistry, Japan
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