Direct and stereospecific interaction of amphidinol 3 with sterol in lipid bilayers

College

College of Science

Department/Unit

Chemistry

Document Type

Article

Source Title

Biochemistry

Volume

53

First Page

3287

Last Page

3293

Publication Date

2014

Abstract

Amphidinol 3 (AM3), a polyhydroxy-polyene metabolite from the dinoflagellate Amphidinium klebsii, possesses potent antifungal activity. Although AM3 permeabilizes phospholipid membranes only in the presence of sterol, the detailed molecular basis by which AM3 recognizes sterols in membranes remains unknown. Here, we investigated the molecular interaction between sterols and AM3 in membranes from the viewpoint of stereospecific molecular recognition using ergosterol, cholesterol, and epicholesterol, which is the 3-OH epimer of cholesterol. Dye leakage assays, surface plasmon resonance experiments, 2H and 31P NMR measurements, and microscopic observations revealed that AM3 directly interacts with membrane sterols through the strict molecular recognition of the stereochemistry of the sterol 3-OH group. The direct interaction enhances the membrane binding efficiency of AM3, which subsequently permeabilizes membranes without altering membrane integrity.

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Digitial Object Identifier (DOI)

https://doi.org/10.1021/bi5002932

Disciplines

Chemistry

Keywords

Dinoflagellates; Antifungal agents; Sterols; Chemical reactions

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