From Antimicrobial Peptides to Antimicrobial Poly(α-amino acid)s.

Abstract

Conventional small-molecule antibiotics are facing a significant challenge of the rapidly developed drug resistance of pathogens. In contrast, antimicrobial peptides (AMPs), an important component for innate host defenses, are now under intensive investigation as a promising antimicrobial agent for combating drug resistant pathogens. Most AMPs can effectively kill a broad spectrum of pathogens via physical disruption of microbial cellular membranes, which is identified to be difficult to develop resistance. However, the clinical applications of AMPs are still greatly limited by several inherent impediments, such as high cost of production, potential hemolysis or toxicity, and liability to proteinase degradation. Recently, cationic poly(α-amino acid)s with structures mimicking the AMPs are found to have excellent antimicrobial activity. These polymers, termed "antimicrobial poly(α-amino acid)s (APAAs)," have some advantages over AMPs, such as easy production and modification, prolonged antimicrobial activity, low cytotoxicity, and enhanced stability to protease degradation. Here, a brief introduction of mechanisms and affecting factors of microbial killing by AMPs is first presented, followed by a systematic illustration of recent advances in design and preparation of biomimetic APAAs and a perspective in this field.