Recent Progress in Antimicrobial Peptides (AMPs) Towards Enhanced Selectivity and Reduced Cytotoxicity by Molecular Engineering

ABSTRACT

Increased prevalence of antimicrobial resistance has led to the urgent need for designing and developing new therapeutic alternatives to conventional antibiotics. Antimicrobial peptides (AMPs) represent a promising class of antimicrobial agents, with broad‐spectrum activity and rapid action, and a low potential to promote antibiotic resistance. This review article synthesizes progress in engineering AMPs to optimize effectiveness in terms of enhancing selectivity for treating infections while minimizing cytotoxicity to host cells. Mechanisms by which AMPs exert their effects, such as disrupting membranes, targeting intracellular portions of the cell, inhibiting biofilm formation, and modulating immune response, will be explored in relation to interactions between AMPs and lipid bilayers. The effects of physicochemical properties (e.g., charge and hydrophobicity), peptide length (number of amino acids), and peptide secondary structure on antimicrobial activity and host compatibility are outlined. An overview will be provided of some of the new design approaches for engineering peptides, including peptide modifications, peptide mimetic structures, hybrid peptides, dendritic AMPs, and the use of computational methods and bioengineering techniques. This review highlights current challenges for AMPs, including stability, toxicity, delivery, and drug development for clinical use.