The effect of tailing lipidation on the bioactivity of antimicrobial peptides and their aggregation tendency

Antimicrobial peptides (AMPs) are potentially powerful alternatives to conventional antibiotics in combating multidrug resistance, given their broad spectrum of activity. They mainly interact with cell membranes through surface electrostatic potentials and the formation secondary structures, resulting permeability destruction target microorganism membranes. Our earlier work showed that two leading AMPs, MSI-78 (4–20) pardaxin (1–22), had potent antimicrobial activity against a range bacteria. It is known attachment moderate-length lipid carbon chains cationic can further improve functionality these enhanced interactions membrane bilayer, inducing curvature, destabilization, potential leakage. Thus, this work, we aimed investigate activity, oligomerization propensity, lipid-membrane binding N-terminal lipidated analogs (1–22). Molecular modeling results suggest aggregation N-lipidated AMPs may impart greater structural stability solution depth bilayer insertion for over parental peptide. experimental computational findings provide insights into how lipidation alter conformations, subsequent effects on functional properties regard self-aggregation behavior, interactions,