具有高效抗MRSA活性的Alpha-Beta杂化多肽聚合物分子刷（英文）

Alpha-beta chimeric polypeptide molecular brushes display potent activity against superbugs-methicillin resistant Staphylococcus aureus

近年来,以耐甲氧西林金黄色葡萄球菌(MRSA)为代表的"超级细菌"不断被发现和扩散,已经严重威胁人类健康,因此,研制新型、高效的抗菌剂迫在眉睫.以宿主防御肽及其模拟物为代表的多肽和聚合物近年来得到广泛关注.而分子刷作为一类独特的聚合物也显示了很多特殊的性能.我们结合前期研究,首次将两种开环聚合体系即β-内酰胺开环聚合和N-羧基环内酸酐(NCA)开环聚合体系相结合,以β多肽为骨架结构进而通过其氨基功能基团进一步引发NCA开环聚合,合成了侧链具有多个聚赖氨酸的α/β杂化多肽聚合物分子刷.这种新型分子刷对多种MRSA菌株均展现出高效的抗菌活性,甚至优于万古霉素.通过扫描电子显微镜(SEM)表征,揭示了α/β杂化多肽聚合物分子刷的抗菌机理与宿主防御肽类似,是通过破坏细菌细胞膜的完整性杀菌.α/β杂化多肽聚合物分子刷高度可调的结构特点和高效的抗菌活性,显示了其在抗菌研究和应用中的潜力.

Staphylococcus aureus(S.aureus)are frequently encountered for both nosocomial infections and community acquired infections,with special concerns on the quick emergence of methicillin resistant S.aureus(MRSA)[1,2].Antibiotics are used extensively to treat these infections[2].However,antimicrobial resistance has been a tremendous challenge against current antibiotic and calls for urgent actions to explore novel antimicrobial agents that are active against MRSA and are less susceptible to antimicrobial resistance than do conventional antibiotics[3–13].Encouraged by the low propensity for microbes to develop antimicrobial resistance,host defense peptides(HDPs)and their synthetic mimics were actively studied[3,4,14–34].Although peptidyl mimics of HDP have variable structures,many of them involved multiple copies ofα-L-lysine to introduce into the molecules positive charges that were critical for the antimicrobial activity[35,36].