title: Membrane binding and permeation by indolicidin analogs studied by a biomimetic lipid/polydiacetylene vesicle assay.
abstract: Membrane binding and relative penetration of indolicidin analogs were studied using lipid/polydiacetylene (PDA) chromatic biomimetic membranes. Colorimetric and fluorescence analyses determined that an indolicidin analog with a proline and tryptophan residue substituted with lysines showed more pronounced bilayer surface interactions, while indolicidin and particularly an indolicidin analog in which all prolines were replaced with alanine residues exhibited deeper insertion into the lipid bilayer. The colorimetric data demonstrated that more pronounced blue-red transitions were observed when the chromatic vesicles incorporated lipopolysaccharide (LPS) within the lipid bilayer, indicating that LPS promoted preferred binding and incorporation of the peptides at the lipid/water interface. The fluorescence quenching experiments further confirmed this outcome. The results indicate that the antibacterial activity of indolicidin most likely requires initial binding to the LPS moieties within bacterial membranes, as well as disruption of the bilayer interface. The degree of hemolysis induced by the analogs, on the other hand, correlated to the extent of penetration into the hydrophobic core of the lipid assembly.
authors.affiliation: Department of Chemistry and Stadler Minerva Center for Mesoscopic Macromolecular Engineering, Ben Gurion University of the Negev, Beersheva 84105, Israel. razj@bgumail.bgu.ac.il
authors.forename: Revital
authors.initials: R
authors.lastname: Halevy
authors.forename: Annett
authors.initials: A
authors.lastname: Rozek
authors.forename: Sofiya
authors.initials: S
authors.lastname: Kolusheva
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
authors.forename: Raz
authors.initials: R
authors.lastname: Jelinek
mesh_terms: D000114:Acetylene / Q000031:analogs & derivatives*; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000378:metabolism*; D032701:Biomimetics; D002463:Cell Membrane Permeability; D002942:Circular Dichroism; D003124:Colorimetry; D004912:Erythrocytes / Q000187:drug effects; D005456:Fluorescent Dyes / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism*; D010714:Phosphatidylethanolamines; D000078789:Polyacetylene Polymer; D011108:Polymers; D053279:Polyynes; D013050:Spectrometry, Fluorescence; D013113:Spin Labels; D014364:Tryptophan / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D005456:Fluorescent Dyes; D008070:Lipopolysaccharides; D008081:Liposomes; D010714:Phosphatidylethanolamines; D000078789:Polyacetylene Polymer; D011108:Polymers; D013113:Spin Labels; C073143:indolicidin; D053279:Polyynes; C082361:polydiacetylene; C042077:N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)phosphatidylethanolamine; D014364:Tryptophan; D000114:Acetylene