期刊
BIOMACROMOLECULES
卷 10, 期 6, 页码 1416-1428出版社
AMER CHEMICAL SOC
DOI: 10.1021/bm900044x
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资金
- Department of Biological and Materials Sciences, University of Michigan, School of Dentistry
A library of amphiphilic random copolymers containing cationic and hydrophobic side chains were prepared by copolymerization of amine-functionalized methacrylate monomers with various ratios of an alkyl methacrylate. Primary or tertiary amine groups, or quaternary ammonium groups, were utilized as the source of cationic charge in each copolymer series. The antimicrobial and hemolytic activities of these copolymers are reported, enabling a systematic assessment of the effect different amine groups exert on the biological activity of the polymers. It was shown that the copolymer composition of amphiphilic copolymers containing primary or tertiary amine groups can be tuned to achieve potent antimicrobial activity while minimizing red blood cell lysis. On the other hand, the copolymers containing quaternary ammonium groups required a greater amount of hydrophobic comonomer to express activity and showed generally lower selectivity for E. coli versus human red blood cells. Potentiometric titration data revealed the fraction of the primary or tertiary amine groups in the polymers, which are deprotonated (basic) at physiological pH. Measurements of the bactericidal and hemolytic activities in buffers of pH varying from 6 to 8 showed the impact of polymer ionization on biological activity. A decrease in the fraction of amine groups that are cationic, from alpha = 1.0 to 0.7, caused an enhancement of antimicrobial and hemolytic activity. As this value was decreased further to alpha = 0.5, loss of activity was observed. The activities of polymers containing quaternary ammonium groups were shown to be pH-independent.
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