Enhancing the stability of antimicrobial peptides: From design strategies to applications

Antimicrobial peptides (AMPs) offer unique advantages due to their membrane-active antimicrobial mechanisms, which reduce the likelihood of resistance development. However, their practical application is hindered by poor stability in vivo, primarily attributed to the presence of high salt concentrations and proteases. To overcome these challenges, this review begins by summarizing the progress of AMPs in practical applications, and then focuses on introducing strategies for designing and optimizing AMPs to enhance their stability. Various approaches are discussed, including the conjugation with protease inhibitors, incorporation of cyclization or nanotechnology to constrain conformational dynamics, optimization of structural parameters of AMPs and so on. Moreover, we examine the intricate relationship between stability and design strategies. Lastly, we provide a comprehensive outlook on the future prospects and challenges in developing highly stable AMPs.