title: Directed peptide assembly at the lipid-water interface cooperatively enhances membrane binding and activity.
abstract: We modified membrane-active peptides with synthetic recognition modules to foster peptide assembly at the lipid-water interface. The designed recognition strategy has been previously reported: tris-cyanuric acid and tris-melamine have been found to bind selectively to each another when membrane-anchored. We designed this interaction to occur between two membrane-active peptides, forming a heteromeric complex at the lipid-water interface that exhibits superior membrane binding and permeation compared to the monomeric peptides, presumably because of the higher avidity of the assembled structure. These conjugates do not assemble appreciably in solution but assemble at the lipid-water interface, with surface binding of the peptide acting cooperatively with molecular recognition to yield improved binding and permeation. Furthermore, we find that specific recognition between tris-cyanuric acid phospholipid (TCA-PE) at low surface concentration and tris-melamine magainin (TMM) or hexa-melamine magainin (HMM) results in highly lytic binding, whereas no binding is detectable in the absence of lipid recognition. These findings suggest a noncovalent strategy to enhance peptide membrane activity, which may lead to the discovery of more potent surface-active agents such as antimicrobials.
authors.affiliation: Department of Chemistry, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Mingming
authors.initials: M
authors.lastname: Ma
authors.forename: Dennis
authors.initials: D
authors.lastname: Bong
mesh_terms: D002942:Circular Dichroism; D008051:Lipid Bilayers / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D008055:Lipids; D010455:Peptides; D014867:Water