Guanylated Polymethacrylates: A Class of Potent AntimicrobialPolymers with Low Hemolytic Activity.

Wehave synthesized a series of copolymers containing both positivelycharged (amine, guanidine) and hydrophobic side chains (amphiphilicantimicrobial peptide mimics). To investigate the structure–activityrelationships of these polymers, low polydispersity polymethacrylatesof varying but uniform molecular weight and composition were synthesized,using a reversible addition–fragmentation chain transfer (RAFT)approach. In a facile second reaction, pendant amine groups were convertedto guanidines, allowing for direct comparison of cation structureon activity and toxicity. The guanidine copolymers were much moreactive against Staphylococcus epidermidisand Candida albicanscompared tothe amine analogues. Activity against Staphylococcusepidermidisin the presence of fetal bovine serumwas only maintained for guanidine copolymers. Selectivity for bacterialover mammalian cells was assessed using hemolytic and hemagglutinationtoxicity assays. Guanidine copolymers of low to moderate molecularweight and hydrophobicity had high antimicrobial activity with lowtoxicity. Optimum properties appear to be a balance between chargedensity, hydrophobic character, and polymer chain length. In conclusion,a suite of guanidine copolymers has been identified that representa new class of antimicrobial polymers with high potency and low toxicity. [ABSTRACT FROM AUTHOR]