Antimicrobial Peptide Mimicking Primary Amine and Guanidine Containing Methacrylamide Copolymers Prepared by Raft Polymerization.
Antimicrobial Peptide Mimicking Primary Amine and Guanidine Containing Methacrylamide Copolymers Prepared by Raft Polymerization.
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DOI：
10.1021/acs.biomac.5b01162
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发表时间：
2015-12-14
影响因子：
6.2
通讯作者：
Morgan SE
中科院分区：
文献类型：
--
作者：
Exley SE;Paslay LC;Sahukhal GS;Abel BA;Brown TD;McCormick CL;Heinhorst S;Koul V;Choudhary V;Elasri MO;Morgan SE
天然存在的抗微生物肽（AMP）显示出消除多种细菌的能力，而对宿主真核细胞没有毒性。已报道含有模拟AMP中发现的赖氨酸和精氨酸组分的部分的合成聚合物显示出对特定细菌的有效性，据称活性机制取决于氨基酸模拟物的性质。为了将两种氨基酸的抗微生物活性结合到单一的水溶性共聚物中，通过水性RAFT聚合制备了一系列含有赖氨酸模拟氨基丙基甲基丙烯酰胺（APMA）和精氨酸模拟胍基丙基甲基丙烯酰胺（GPMA）的共聚物。用不同比例的共聚单体制备共聚物，聚合度为35-40，分子量分布窄，以模拟天然存在的AMP。在不同盐浓度的条件下测定了对革兰氏阴性菌和革兰氏阳性菌的抗微生物活性。通过红细胞溶血和MCF-7细胞MTT试验评估对哺乳动物细胞的毒性。观察到APMA均聚物和共聚物与低浓度的GPMA对所有测试细菌的抗微生物活性，对哺乳动物细胞具有低毒性。
Naturally occurring antimicrobial peptides (AMPs) display the ability to eliminate a wide variety of bacteria, without toxicity to the host eukaryotic cells. Synthetic polymers containing moieties mimicking lysine and arginine components found in AMPs have been reported to show effectiveness against specific bacteria, with the mechanism of activity purported to depend on the nature of the amino acid mimic. In an attempt to incorporate the antimicrobial activity of both amino acids into a single water-soluble copolymer, a series of copolymers containing lysine mimicking aminopropyl methacrylamide (APMA) and arginine mimicking guanadinopropyl methacrylamide (GPMA) were prepared via aqueous RAFT polymerization. Copolymers were prepared with varying ratios of the comonomers, with degree of polymerization of 35–40 and narrow molecular weight distribution to simulate naturally occurring AMPs. Antimicrobial activity was determined against Gram-negative and Gram-positive bacteria under conditions with varying salt concentration. Toxicity to mammalian cells was assessed by hemolysis of red blood cells and MTT assays of MCF-7 cells. Antimicrobial activity was observed for APMA homopolymer and copolymers with low concentrations of GPMA against all bacteria tested, with low toxicity toward mammalian cells.