Disruption of Interactions between Hydrophobic Residues on Nonpolar Faces is a Key Determinant in Decreasing Hemolysis and Increasing Antimicrobial Activities of a-Helical Amphipathic Peptides

摘要

Antimicrobial peptides (AMPs) are naturally occurring substances that have innate immunities against pathogens in species ranging from insects to mammals. a-Helical cationic antimicrobial peptides (CAPs) are a subfamily of AMPs that possess positively charged residues and high propensities for a-helicity in membrane environments. These peptides have amphiphilic (or amphipathic) properties due to the presence of both positively charged as well as hydrophobic residues. A proper balance of amphiphilicity enables CAPs to facilitate disruption of pathogenic membranes, which results in cell lysis. The mechanism through which these peptides disrupt zwitterionic eu-karyotic membranes is different from the mechanism through which they act on negatively charged prokaryotic membranes. However, high α-helical propensity under membrane conditions and a reasonable hydrophobicity are the main factors governing the ability of CAPs to destroy host (eukaryotic) cell membranes.