• Meagher, Laurence
• Griesser, Hans
• Michl, Thomas
• Haeussler, Matthias
• Locock, Katherine

Abstract

Host defence antimicrobial peptides (AMPs) are a promising lead in the search for novel antibiotics. Many of these peptides have been shown to exhibit broad spectrum antibacterial ability, low toxicity toward human cells and little susceptibility to currently known mechanisms of bacterial resistance1,2. Their use has been somewhat limited, however, as proteins are typically pharmacokinetically unstable and large scale production costs expensive. Several AMP-mimicking polymers have 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. The synthesis of these polymers was achieved using Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization, followed by a base-catalyzed guanylation (Scheme 1). A range of random copolymers of methylmethacrylate (MMA) and 2-guanidinoethyl methacrylate (2-GEMA) were produced, varying monomer ratio (hydrophobic character) and polymer length, thus allowing the systematic investigation of structure-activity relationships. 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), fungal strains (eg. C. albicans) 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