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Title: Membrane interaction of a new synthetic antimicrobial lipopetide sp-85 with broad spectrum activity
Author: Grau Campistany, Ariadna
Pujol Cubells, Montserrat
Marqués Villavecchia, Ana M.
Manresa Presas, Ma. Ángeles (María Ángeles)
Rabanal Anglada, Francesc
Cajal Visa, Yolanda
Keywords: Síntesi de pèptids
Peptide synthesis
Issue Date: 8-Nov-2014
Publisher: Elsevier B.V.
Abstract: Antimicrobial peptides offer a new class of therapeutic agents to which bacteria may not be able todevelop genetic resistance, since their main activity is in the lipid component of the bacterial cell mem-brane. We have developed a series of synthetic cationic cyclic lipopeptides based on natural polymyxin,and in this work we explore the interaction of sp-85, an analog that contains a C12 fatty acid at theN-terminus and two residues of arginine. This analog has been selected from its broad spectrum antibac-terial activity in the micromolar range, and it has a disruptive action on the cytoplasmic membrane ofbacteria, as demonstrated by TEM. In order to obtain information on the interaction of this analog withmembrane lipids, we have obtained thermodynamic parameters from mixed monolayers prepared withPOPG and POPE/POPG (molar ratio 6:4), as models of Gram positive and Gram negative bacteria, respec-tively. Langmuir<br>Blodgett films have been extracted on glass plates and observed by confocal microscopy,and images are consistent with a strong destabilizing effect on the membrane organization induced bysp-85. The effect of sp-85 on the membrane is confirmed with unilamelar lipid vesicles of the same com-position, where biophysical experiments based on fluorescence are indicative of membrane fusion andpermeabilization starting at very low concentrations of peptide and only if anionic lipids are present.Overall, results described here provide strong evidence that the mode of action of sp-85 is the alterationof the bacterial membrane permeability barrier.
Note: Versió postprint del document publicat a:
It is part of: Colloids and Surfaces A-Physicochemical and Engineering Aspects, 2014
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ISSN: 0927-7757
Appears in Collections:Articles publicats en revistes (Biologia, Sanitat i Medi Ambient)

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