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Interaction of Acylated and Substituted Antimicrobial Peptide Analogs with Phospholipid–Polydiacetylene Vesicles. Correlation with their Biological Properties
Author(s) -
Siano Alvaro,
Húmpola María V.,
Rey María C.,
Simonetta Arturo,
Tonarelli Georgina G.
Publication year - 2011
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2011.01099.x
Subject(s) - dipalmitoylphosphatidylcholine , chemistry , vesicle , peptide , antimicrobial , staphylococcus aureus , phospholipid , biochemistry , biological activity , biological membrane , listeria monocytogenes , bacteria , membrane , in vitro , organic chemistry , biology , phosphatidylcholine , genetics
A series of peptide analogs based on region 6–22 of Plantaricin 149 sequence were synthesized. The interaction between these analogs and phospholipid–polydiacetylene vesicles was investigated to evaluate the ability of the bioassay to detect differences in the interaction of the peptides with dipalmitoylphosphatidylglycerol and dipalmitoylphosphatidylcholine vesicles, associated with amino acid substitution and N‐terminal conjugation of the sequences with short fatty acids (8 and 12 carbon atoms). Fatty acid conjugation of peptides with low antimicrobial activity resulted in lipopeptides with improved activity against strains of Staphylococcus aureus and Listeria monocytogenes . The length of the fatty acid determined the bacterial specificity, and the conjugation with n‐octanoic acid yielded the most active analog (C8‐CT) against Staphylococcus aureus strain (MIC: 1.0 μ m ) while the conjugation with n‐dodecanoic acid (C12‐CT) was optimal for Listeria monocytogenes strain (MIC: 2.0 μ m ). In contrast, the substitution of Phe by Trp had an unfavorable effect on the antimicrobial activity. Hemolysis tests and membrane interaction studies with dipalmitoylphosphatidylcholine–polydiacetylene vesicles showed that lipopeptides interact to a greater extent with both biological and biomimetic membranes. Also, a good correlation was found between antimicrobial activity against Staphylococcus aureus strain and % colorimetric response values with dipalmitoylphosphatidylglycerol–polydiacetylene vesicles.