CONICET | Buscador de Institutos y Recursos Humanos

Cationic antimicrobial peptides (CAMPs) represent important self defense molecules in many organisms, including humans. These peptides have a broad spectrum of activities, killing or neutralizing many Gram-negative and Gram-positive bacteria. The emergence of multidrug resistant microbes has stimulated research on the development of alternative antibiotics. In this regard, it is important to identify the AMPs features necessary for the display activity, enabling the design of more potent and simpler, i.e. less expensive, AMPs. In this context the aim of this work was to evaluate the membrane interaction of a AMP p6.2 and its parent peptide without antimicrobial activity. The interactions of peptides, with liposomes and lipid monolayers were evaluated by monitoring the changes in the fluorescence of the Trp residues and the variation of the monolayers surface pressure. Results obtained with both techniques revealed a significant higher affinity of peptide 6.2 in comparison with parent peptide 6. The position of the peptides in the membrane was also studied, by using different Trp quenchers (Acrylamide, 5NS and 16NS). In this case both peptides showed a final location slightly inserted in the acyl core of the membrane. However, peptide 6.2 seems to adopt a slightly more shallow position. Finally the affinity of the peptides for erythrocyte membrane was evaluated as indication of possible hemolytic activity founding that peptide 6 exhibits a higher affinity toward erythrocyte membrane than 6.2 in a good agreement with hemolytic data. Overall data obtained in this work allow us to conclude that membrane affinity especial toward negatively charged lipid is a key factor in the final antimicrobial activity, offering a rational basis for the design of improved AMPs, since they suggest that maximizing antiviral activity requires finding the proper balance of bacterial membrane affinity and low hemolytic effects.

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