• Locock, Katherine

Abstract

Increasing antibiotic resistance has spurred interest in the development of novel antimicrobial agents with increased potency and/or a decreased susceptibility to the onset of microbial resistance. Host defence antimicrobial peptides (AMPs) are a promising lead in this search, as many have been shown to exhibit broad spectrum antibacterial ability, low toxicity toward human cells and little susceptibility to currently known mechanisms of bacterial resistance. Their use has been somewhat limited, however, as proteins are typically chemically unstable and can be expensive to produce in large quantities. Several AMP-mimicking polymers have hence been developed to overcome such issues. These polymers are able to retain the essential facially amphiphilic secondary structure of AMPs, while being cheaper and easier produced and chemically manipulated.This study describes a novel class of AMP-mimicking polymers, the guanylated polymethacrylates. A range of random copolymers of methyl methacrylate (MMA) and 2 guanidinoethyl methacrylate(2-GEMA) were produced using a Reversible Addition-Fragmentation chain Transfer (RAFT) approach, varying monomer ratio and polymer length. A number of these poly(MMA-GEMA) copolymers exhibited potent antimicrobial effects (MIC = 10 μg/ml) against gram positive strains of bacteria (eg. S. epidermidis) and low toxicity towards human blood cells.Data produced from this study will not only help to elucidate the structure-activity relationships governing antimicrobial polymethacylates but may also reveal a lead for the development of novel agents to combat the growing threat of antibiotic resistance.

Topics

• random
• copolymer
• toxicity
• susceptibility
• random copolymer