Guanylated Polymethacrylates: A Class of Potent Antimicrobial Polymers with Low Hemolytic Activity

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• 作者：Katherine E. S. Locock ; Thomas D. Michl ; Jules D. P. Valentin ; Krasimir Vasilev ; John D. Hayball ; Yue Qu ; Ana Traven ; Hans J. Griesser ; Laurence Meagher ; Matthias Haeussler
• 刊名：Biomacromolecules
• 出版年：2013
• 出版时间：November 11, 2013
• 年：2013
• 卷：14
• 期：11
• 页码：4021-4031
• 全文大小：481K
• 年卷期：v.14,no.11(November 11, 2013)
• ISSN：1526-4602

文摘

We have synthesized a series of copolymers containing both positively charged (amine, guanidine) and hydrophobic side chains (amphiphilic antimicrobial peptide mimics). To investigate the structure鈥揳ctivity relationships of these polymers, low polydispersity polymethacrylates of varying but uniform molecular weight and composition were synthesized, using a reversible addition鈥揻ragmentation chain transfer (RAFT) approach. In a facile second reaction, pendant amine groups were converted to guanidines, allowing for direct comparison of cation structure on activity and toxicity. The guanidine copolymers were much more active against Staphylococcus epidermidis and Candida albicans compared to the amine analogues. Activity against Staphylococcus epidermidis in the presence of fetal bovine serum was only maintained for guanidine copolymers. Selectivity for bacterial over mammalian cells was assessed using hemolytic and hemagglutination toxicity assays. Guanidine copolymers of low to moderate molecular weight and hydrophobicity had high antimicrobial activity with low toxicity. Optimum properties appear to be a balance between charge density, hydrophobic character, and polymer chain length. In conclusion, a suite of guanidine copolymers has been identified that represent a new class of antimicrobial polymers with high potency and low toxicity.