title: pH-Dependent lytic peptides discovered by phage display.
abstract: Lipid membranes compartmentalize eukaryotic cells and separate the cell interior from the extracellular milieu. So far, studies of peptide and protein interactions with membranes have largely been limited to naturally occurring peptides or to sequences designed on the basis of structural information and biophysical parameters. To expand on these studies, utilizing a system with minimal assumptions, we used phage-display technology to identify 12 amino acid-long peptides that bind to liposomes at pH 5.0 but not at pH 7.5. Of the nineteen peptides discovered, three were able to cause leakage of liposome contents. Multivalent presentation of these membrane-active peptides by conjugation onto poly(l-Lysine) enhanced their lytic potential. The secondary structures were analyzed by circular dichroism in aqueous 2,2,2-trifluoroethanol and in buffered aqueous solutions, both in the presence and absence of liposomes. Two of the three lytic peptides show alpha helical profiles, whereas none of the nonlytic peptides formed stable secondary structures. The diverse characteristics of the peptides identified in this study demonstrate that phage-displayed peptide library screens on lipid membranes result in the discovery of nonclassical membrane-active peptides, whose study will provide novel insights into peptide-membrane interactions.
authors.affiliation: Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hirosue
authors.forename: Thomas
authors.initials: T
authors.lastname: Weber
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary
chemical_list: D008081:Liposomes; D019151:Peptide Library; D010455:Peptides