Role and modulation of the secondary structure of antimicrobial peptides to improve selectivity

Since the development of bacterial resistance, the decreasing effectiveness of antibiotics is becoming one of the most critical problems worldwide. Novel antibacterial agents are urgently needed to prevent humanity from falling back into the “post-antibiotic era”. As an important part of the innate immune system, antimicrobial peptides (AMPs) are one of the most promising antibacterial agents showing broad-spectrum activity against bacteria and low propensity for drug resistance. However, the shortcomings of AMPs, such as high toxicity and easy digestion by proteases, limit their clinical application. This review mainly focuses on the effect of the secondary structure on the antimicrobial activity and cytotoxicity of AMPs and the strategies of designing conformationally transitionable AMPs with improved selectivity towards bacteria.