title: Translocation of protegrin I through phospholipid membranes: role of peptide folding.
abstract: The protegrin PG-1, belonging to the family of beta-stranded antimicrobial peptides, exerts its activity by forming pores in the target biological membranes. Linear analogues derived from PG-1 do not form pores in the phospholipid membranes and have been used successfully to deliver therapeutic compounds into eucaryotic cells. In this paper, the translocation of PG-1 and of a linear analogue through artificial phospholipid membranes was investigated, leading to a possible mechanism for the activity of these peptidic vectors. We report here that [12W]PG-1, a fluorescent analogue of PG-1, is able to translocate through lipid bilayers and we demonstrate that this property depends on its secondary structure. Our results agree with the recent mechanism proposed for the translocation and permeabilisation activities of several helical and beta-stranded peptides. In addition, our data corroborate recent work suggesting that certain protegrin-derived vectors enter into endothelial cells by adsorptive-mediated endocytosis.
authors.affiliation: Synt:em, Parc Scientifique Georges Besse, 3000 Nîmes, France. gdrin@syntem.com
authors.forename: Guillaume
authors.initials: G
authors.lastname: Drin
authors.forename: Jamal
authors.initials: J
authors.lastname: Temsamani
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides; D002460:Cell Line; D002463:Cell Membrane Permeability; D002942:Circular Dichroism; D003619:Dansyl Compounds; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D008051:Lipid Bilayers / Q000737:chemistry*; D008969:Molecular Sequence Data; D010714:Phosphatidylethanolamines; D010743:Phospholipids / Q000737:chemistry; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D013050:Spectrometry, Fluorescence
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D003619:Dansyl Compounds; D005456:Fluorescent Dyes; D008051:Lipid Bilayers; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D011506:Proteins; C094880:protegrin-1; C056851:N-5-dimethylaminonaphthalene-1-sulfonyl-dipalmitoylphosphatidylethanolamine