6533b7d0fe1ef96bd125af4f

RESEARCH PRODUCT

Membrane-Perturbing Activities of KL4-Related Surfactant Peptides

subject

description

KL4 is a 21-residue peptide proposed as a potential substitute of pulmonary surfactant protein SP-B in synthetic surfactants, intended for the treatment of respiratory pathologies. The peptide, composed by leucines interrupted by lysine every four residues, was synthesized to simulate C-terminal amphipathic helical segments of SP-B. Once incorporated into lipid-protein complexes, KL4 promotes formation of interfacial films that produce and maintain surface tensions below 5 mN/m during compression-expansion cycling. Although KL4 was designed as an amphipathic helix at the membrane surface, the data on orientation and interactions of the peptide in membranes are contradictory. In the present work the surface activity and interaction with membranes of KL4 was compared with the behavior of two other peptides, KL2A2 and KL4PQ, to gain information about the properties defining the potential of KL4 as surfactant additive.The surface activity of the different peptides in lipid suspensions mimicking surfactant composition (DPPC/POPC/POPG 50:25:15 w/w/w), was analyzed in a captive bubble surfactometer (CBS). Only lipid suspensions containing KL4 adsorbed to the air-liquid interface with kinetics comparable to those containing SP-B, with KL4PQ and specially KL2A2 showing less activity. The interaction of the three peptides with membranes was analyzed by DSC, Laurdan fluorescence and ATR-FTIR. Perturbations induced by peptides on the structure and permeability of giant unilamellar vesicles (GUVs) were also analyzed and compared with the behavior of natural SP-B.The results indicate that the extent of penetration of the peptides in bilayers and their ability to perturb membrane structure correlate with their different interfacial activity.