Bioinspired Polymers: Antimicrobial Polymethacrylates

Abstract

Naturally occurring antimicrobial peptides have been honed by evolution over millions of years to give highly safe and efficacious antimicrobials that form part of many organisms’ immune systems. By studying these peptides to identify key aspects of structure and composition, suitable synthetic polymer mimics can be designed that hold potential as anti-infective agents. This review focusses on an important aspect of peptide mimicry, that of replicating the chemical functionality provided by key amino acids present in antimicrobial peptides. These include polymethacrylate mimics of arginine-rich and tryptophan-rich peptides. Systematic investigation of the structure–activity relationships of these polymers identifies the guanidine based poly(methylmethacrylate-co-2-guanidinoethyl methacrylate) (pMMA-co-GEMA) copolymers with low molecular weight and low methyl content as having superior activity profiles when compared with all other combinations. Unique antibiofilm activity of these polymers is also revealed in in vitro testing against monomicrobial and polymicrobial biofilms of the bacteria Staphylococcus aureus and the fungus Candida albicans. This highlights Mother Nature as an important resource in drug development and identifies the arginine-mimicking polymethacrylates as important leads for the development of a new generation of antimicrobial agents to tackle resistance.