Positive Charge-Concentrated Dimeric Lipopeptides with Enhanced Protease Resistance: A Potential Solution for Systemic Bacterial Infections

Antimicrobial peptides (AMPs) show potential as antibiotic alternatives for bacterial infections; nevertheless, the susceptibility to proteases limits their broader utilization. This study developed engineered lipopeptides using antienzymolysis modifications and cysteine (Cys)-dimerization strategy. As the key parameters for the functioning of AMPs, hydrophobicity and positive charges were concentrated within the peptide sequence by adjusting the intermolecular disulfide bond placement to study their distribution effects. Their centralization in the sequence induces a differential propensity of engineered lipopeptides toward bacterial membranes. Positive charge-concentrated dimeric lipopeptide (C-C