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Issue 5, 2015
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Membrane-interacting properties of the functionalised fatty acid moiety of muraymycin antibiotics

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Abstract

Functional insights into bioactive natural products with medicinal potential are often hindered by their structural complexity. We herein report a simplified model system to investigate the functional significance of a structural motif of biologically potent muraymycin antibiotics of the A-series. These compounds have a highly unusual ω-guanidinylated fatty acid moiety, which has been proposed to mediate membrane penetration, thus enabling the interaction of A-series muraymycins with their intracellular target MraY. Our assay was based on a synthetic conjugate of this fatty acid structure with a negatively charged fluorophore lacking membrane permeability. Using this conjugate, immobilised giant unilamellar lipid vesicles and confocal laser scanning fluorescence microscopy, we demonstrated that the attachment of the ω-N-hydroxy-guanidinyl fatty acid unit led to an enhanced uptake of the fluorophore into the vesicles. This represents the first experimental evidence of this unusual structural motif's functional relevance for the parent natural product, which may support the future design of novel muraymycin analogues.

Graphical abstract: Membrane-interacting properties of the functionalised fatty acid moiety of muraymycin antibiotics

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Supplementary files

Article information


Submitted
18 Nov 2014
Accepted
06 Mar 2015
First published
06 Mar 2015

This article is Open Access

Med. Chem. Commun., 2015,6, 879-886
Article type
Concise Article

Membrane-interacting properties of the functionalised fatty acid moiety of muraymycin antibiotics

O. Ries, C. Carnarius, C. Steinem and C. Ducho, Med. Chem. Commun., 2015, 6, 879
DOI: 10.1039/C4MD00526K

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