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Recognition of Membrane Sterols by Polyene Antifungals Amphotericin B and Natamycin, A 13C MAS NMR Study

Ciesielski, F; Griffin, DC; Loraine, J; Rittig, M; Delves-Broughton, J; Bonev, BB; (2016) Recognition of Membrane Sterols by Polyene Antifungals Amphotericin B and Natamycin, A 13C MAS NMR Study. Frontiers in Cell and Developmental Biology , 4 (57) 10.3389/fcell.2016.00057. Green open access

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Abstract

The molecular action of polyene macrolides with antifungal activity, amphotericin B and natamycin, involves recognition of sterols in membranes. Physicochemical and functional studies have contributed details to understanding the interactions between amphotericin B and ergosterol and, to a lesser extent, with cholesterol. Fewer molecular details are available on interactions between natamycin with sterols. We use solid state 13C MAS NMR to characterize the impact of amphotericin B and natamycin on mixed lipid membranes of DOPC/cholesterol or DOPC/ergosterol. In cholesterol-containing membranes, amphotericin B addition resulted in marked increase in both DOPC and cholesterol 13C MAS NMR linewidth, reflecting membrane insertion and cooperative perturbation of the bilayer. By contrast, natamycin affects little either DOPC or cholesterol linewidth but attenuates cholesterol resonance intensity preferentially for sterol core with lesser impact on the chain. Ergosterol resonances, attenuated by amphotericin B, reveal specific interactions in the sterol core and chain base. Natamycin addition selectively augmented ergosterol resonances from sterol core ring one and, at the same time, from the end of the chain. This puts forward an interaction model similar to the head-to-tail model for amphotericin B/ergosterol pairing but with docking on opposite sterol faces. Low toxicity of natamycin is attributed to selective, non-cooperative sterol engagement compared to cooperative membrane perturbation by amphotericin B.

Type: Article
Title: Recognition of Membrane Sterols by Polyene Antifungals Amphotericin B and Natamycin, A 13C MAS NMR Study
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fcell.2016.00057
Publisher version: http://doi.org/10.3389/fcell.2016.00057
Language: English
Additional information: © 2016 Ciesielski, Griffin, Loraine, Rittig, Delves-Broughton and Bonev. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: Antimicrobials, antifungals, membranes, cholesterol, ergosterol, 13C solid state MAS NMR, receptor recognition
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
URI: http://discovery.ucl.ac.uk/id/eprint/1509186
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