• Locock, Katherine

Abstract

Host defence antimicrobial peptides (AMPs) are a promising lead in the search for novel antibiotics. These are naturally produced by organisms to defend against the invasion of foreign microbes and 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 pharmacokinetically unstable and their large scale production can be expensive. Based on this lead, a number of AMP-mimicking synthetic polymers have been developed by several research groups. Polymers have benefits over peptides as they are typically cheaper and easier to produce and manipulate chemically, as well as being more amenable to integration into drug delivery systems and medical devices.This study describes a novel class of AMP-mimicking polymers, the guanylated polymethacrylates. A range of random copolymers of methyl methacrylate (MMA) and 2 aminoethyl methacrylate (2-AEMA) were produced using a Reversible Addition-Fragmentation chain Transfer (RAFT) approach, followed by base-catalyzed guanylation to give the final poly(2-GEMA-MMA) series.Of these, a number displayed potent actions against bacteria (MIC = 10 ug/ml for S. epidermidis) and fungi (MIC = 8ug/ml for C. albicans) concordant with low toxicity towards human red blood cells. A discussion of the structure-activity governing these agents and identification of optimal polymer composition will be discussed.

Topics

• random
• copolymer
• toxicity
• susceptibility
• random copolymer