title: Revisiting peptide amphiphilicity for membrane pore formation.
abstract: It has previously been shown that an amphipathic de novo designed peptide made of 10 leucines and four phenylalanines substituted with crown ethers induces vesicle leakage without selectivity. To gain selectivity against negatively charged dimyristoylphosphatidylglycerol (DMPG) bilayers, one or two leucines of the peptide were substituted with positively charged residues at each position. All peptides induce significant calcein leakage of DMPG vesicles. However, some peptides do not induce significant leakage of zwitterionic dimyristoylphosphatidylcholine vesicles and are thus active against only bacterial model membranes. The intravesicular leakage is induced by pore formation instead of membrane micellization. Nonselective peptides are mostly helical, while selective peptides mainly adopt an intermolecular β-sheet structure. This study therefore demonstrates that the position of the lysine residues significantly influences the secondary structure and bilayer selectivity of an amphipathic 14-mer peptide, with β-sheet peptides being more selective than helical peptides.
authors.affiliation: Département de chimie, Regroupement québécois de recherche sur la fonction, la structure et l'ingénierie des protéines, Centre de recherche sur les matériaux avancés, Université Laval, Québec, Québec, Canada G1V 0A6.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Lorin
authors.forename: Mathieu
authors.initials: M
authors.lastname: Noël
authors.forename: Marie-Ève
authors.initials: MÈ
authors.lastname: Provencher
authors.forename: Vanessa
authors.initials: V
authors.lastname: Turcotte
authors.forename: Carole
authors.initials: C
authors.lastname: Masson
authors.forename: Sébastien
authors.initials: S
authors.lastname: Cardinal
authors.forename: Patrick
authors.initials: P
authors.lastname: Lagüe
authors.forename: Normand
authors.initials: N
authors.lastname: Voyer
authors.forename: Michèle
authors.initials: M
authors.lastname: Auger
mesh_terms: D000595:Amino Acid Sequence; D004134:Dimyristoylphosphatidylcholine / Q000378:metabolism; D005452:Fluoresceins / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D010539:Permeability; D010715:Phosphatidylglycerols / Q000378:metabolism; D017433:Protein Structure, Secondary; D013501:Surface-Active Agents / Q000737:chemistry* / Q000378:metabolism
chemical_list: D005452:Fluoresceins; D008051:Lipid Bilayers; D008081:Liposomes; D010455:Peptides; D010715:Phosphatidylglycerols; D013501:Surface-Active Agents; C002773:dimyristoylphosphatidylglycerol; D004134:Dimyristoylphosphatidylcholine; C007740:fluorexon