title: Membrane interactions of synthetic peptides with antimicrobial potential: effect of electrostatic interactions and amphiphilicity.
abstract: Cationic antimicrobial peptides are considered promising candidates to complement currently used antibiotics, which are less effective against increasingly resistant pathogens. To determine the mechanism of action of these peptides, a better understanding of each molecular determinant involved in their membrane interactions is of great importance. In this study, we have focused on the role of electrostatic interactions and amphiphilicity on the membrane interactions since the large majority of natural antimicrobial peptides are cationic. Therefore, cationic and anionic peptides have been prepared based on a model 14-mer peptide. The latter is a synthetic peptide composed of ten leucines and four phenylalanines, which are modified by the addition of the crown ether. Infrared spectroscopy results indicate that the position of substitution is the main determinant involved in the secondary structure adopted by the peptides, and not the charge of the substituted residues. Fluorescence vesicle leakage assays indicate, however, differences between the ability of cationic and anionic peptides to induce calcein release in zwitterionic and anionic lipid vesicles, suggesting an importance of electrostatic interactions and repulsions. Finally, (31)P NMR results indicate that the vesicle morphologies is not significantly affected by the interactions with both cationic and anionic peptides but that their effect on lipid bilayers is mainly determined by their secondary structure. This study therefore indicates that the membrane interactions of model 14-mer peptides are mainly governed by their secondary structure, which depends on the position of substitution, and not the charge of the residues.
authors.affiliation: Department of Chemistry, Regroupement québécois de recherche sur la fonction, la structure et l'ingénierie des protéines (PROTEO), Centre de recherche sur les matériaux avancés (CERMA), Centre québécois sur les matériaux fonctionnels (CQMF), Université Laval, Quebec, QC, G1V 0A6, Canada.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Fillion
authors.forename: Geneviève
authors.initials: G
authors.lastname: Valois-Paillard
authors.forename: Aurélien
authors.initials: A
authors.lastname: Lorin
authors.forename: Mathieu
authors.initials: M
authors.lastname: Noël
authors.forename: Normand
authors.initials: N
authors.lastname: Voyer
authors.forename: Michèle
authors.initials: M
authors.lastname: Auger
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D019265:Spectroscopy, Near-Infrared; D055672:Static Electricity
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D008565:Membrane Proteins