Roles of Hydrophobicity and Charge Distribution of Cationic Antimicrobial Peptides in Peptide-Membrane Interactions

• DOI: 10.1074/jbc.m111.303602
• Publication Date: 2012-01-18T04:56:13Z
• Authors: Lois M. Yin; Michelle A. Edwards; Jessica Li; Christopher M. Yip; Charles M. Deber
• Keywords: 0301 basic medicine; 03 medical and health sciences; Bacteria; Erythrocyte Membrane; Humans; Membranes, Artificial; Hemolysis; Hydrophobic and Hydrophilic Interactions; Protein Structure, Secondary; Antimicrobial Cationic Peptides

Cationic antimicrobial peptides (CAPs) occur as important innate immunity agents in many organisms, including humans, and offer a viable alternative to conventional antibiotics, they physically disrupt the bacterial membranes, leading membrane lysis eventually cell death. In this work, we studied biophysical microbiological characteristics of designed CAPs varying hydrophobicity levels charge distributions by variety biochemical approaches, in-tandem atomic force microscopy, attenuated total reflection-FTIR, CD spectroscopy, SDS-PAGE. Peptide structural properties were correlated with their membrane-disruptive abilities activities. lipid model time-dependent increase aggregated β-strand-type structure relatively high (such KKKKKKALFALWLAFLA-NH(2)) was essentially absent lower KKKKKKAAFAAWAAFAA-NH(2)). Redistribution positive charges placing three Lys residues at both termini while maintaining identical sequences minimized self-aggregation above dimer level. Peptides containing four Leu destructive mammalian whereas those corresponding Ala not. This finding mirrored hemolysis studies human erythrocytes, where Ala-only displayed virtually no up 320 μM, but four-Leu induced 40-80% same concentration range. All strong activity against Pseudomonas aeruginosa (minimum inhibitory concentrations 4-32 μM). The overall findings suggest optimum routes balancing peptide distribution that allow efficient penetration disruption membranes without damage (host) membranes.