Peptide-membrane interaction analysis of an improved antimicrobial peptide derived from the 107-115 hLz fragment

IANNUCCI, NANCY BEATRIZ; HOLLMANN, AXEL; DIAZ, MARÍA R.; CASCONE, OSVALDO; ALBERICIO, FERNANDO; DISALVO, ANÍBAL

San Diego

Simposio; 22nd American Peptide Symposium; 2011

American Peptide Society

  Antimicrobial peptides (AMPs) are produced by almost all species of living beings as a component of their innate non-specific defense against infections [1]. AMPs are typically short peptides with consensus amphiphilic attributes represented by positively charged and hydrophobic amino acids. The lethal step in most cationic AMPs is the disruption of the microbial plasma membrane; this process is accomplished in two steps: membrane binding, mainly governed by electrostatic interactions, and membrane insertion/permeation, related to the hydrophobicity of the peptide and its capacity of partitioning into the plasma membrane [2]. AMPs are very important resources for human therapeutics as lead compounds to counteract the drug resistance development. An improved analog derived from the 107-115 human lysozyme (107-115 hLz) fragment was developed by sequential substitutions of both alanine residues (108 and 111). The sequence of 107-115 hLz peptide is: RAWVAWRNR-NH2. The novel peptide [K108W111]107-115 hLz resulted in a 20-fold increase in the anti-staphylococcal activity and its hemolytic activity resulted significant at 10-fold its MIC [3]. This analog displays an additional positive charge near the N-terminus and an extra Trp residue at the center of the molecule, thus suggesting that this constellation improves its interaction with the bacterial membrane. In order to understand the role of this arrangement in the membrane interaction, studies with model bacterial membranes composed by staphylococcal-isolated lipids and synthetic saturated phosphatidylcholines and phosphatidylethanolamines (DMPC and DMPE) were carried out.