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

IANUCCI, N; HOLLMANN, A; DIAZ, MR; CASCONE, O; ALBERICIO, F; DISALVO, EA

San Diego

Simposio; Twenty-Second American Peptide Symposium; 2011

American Peptide Society

An improved analog derived from the 107-115 hLz fragment was develop by sequential substitutions of both alanine residues (108 and 111). The novel peptide results in a 20 fold increase in the anti-staphylococcal activity and its hemolytic activity becomes significant at 10 fold its MIC. This analog displays an additional positive charge near the N-terminus (108) and an extra Trp residue at the center of the molecule (111), 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 were carried out. The interaction of the both peptides, 107-115 hLz and the novel analog, with lipid monolayers, was studied by in Langmuir though following the variation of the surface pressure at constant area and temperature. The changes of surface pressures at different initial pressures were comparatively analyzed on lipids extracted from Staphylococcus aureus ATCC 29213 and DMPC, DMPE synthetics lipids. In monolayers preformed with lipids extracted from bacteria, the novel analog peptide was able to induce highest changes in the surface pressure at low initial pressures (less than 25 mN/m) in comparison to the unmodified 107-115 hLz which seems not to affect the different initial pressures. These different behaviors of both peptides were also observed in lipid monolayers prepared with synthetic saturated phosphatidylcholines and phsopahtidylethanolamines.