The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions

Bacterial infections caused by ‘superbugs’ are increasing globally, and conventional antibiotics are becoming less effective against these bacteria, such that we risk entering a post-antibiotic era. In recent years, antimicrobial peptides (AMPs) have gained significant attention for their clinical potential as a new class of antibiotics to combat antimicrobial resistance. In this review, we discuss several facets of AMPs including their diversity, physicochemical properties, mechanisms of action, and effects of environmental factors on these features. This review outlines various chemical synthetic strategies that have been applied to develop novel AMPs, including chemical modifications of existing peptides, semi-synthesis, and computer-aided design. We will also highlight novel AMP structures, including hybrids, antimicrobial dendrimers and polypeptides, peptidomimetics, and AMP–drug conjugates and consider recent developments in their chemical synthesis.
This review discusses the diversity of structure and physicochemical properties of antimicrobial peptides and their derivatives, various chemical synthetic strategies that have been applied in their development, and how this links to their activity.