Recent advances in design of antimicrobial peptides and polypeptides toward clinical translation

Abstract

The recent outbreaks of infectious diseases caused by multidrug-resistant pathogens have sounded a piercing alarm for the need of new effective antimicrobial agents to guard public health. Among different types of candidates, antimicrobial peptides (AMPs) and the synthetic mimics of AMPs (SMAMPs) have attracted significant enthusiasm in the past thirty years, due to their unique membrane-active antimicrobial mechanism and broad-spectrum antimicrobial activity. The extensive research has brought many drug candidates into clinical and pre-clinical development. Despite tremendous progresses have been made, several major challenges inherent to current design strategies have slowed down the clinical translational development of AMPs and SMAMPs. However, these challenges also triggered many efforts to redesign and repurpose AMPs. In this review, we will first give an overview on AMPs and their synthetic mimics, and then discuss the current status of their clinical translation. Finally, the recent advances in redesign and repurposing AMPs and SMAMPs are highlighted.

Keywords: Antibiotic resistance; Antimicrobial peptides; Clinical translation; Combination therapy; Infection-responsive peptides; Membrane-active antimicrobial mechanism; Nano-antimicrobials; Radially amphiphilic conformation; Small synthetic mimics of antimicrobial peptides.