Tuning the hemolytic and antibacterial activities of amphiphilic polynorbornene derivatives
Tuning the hemolytic and antibacterial activities of amphiphilic polynorbornene derivatives
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DOI：
10.1021/ja045664d
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发表时间：
2004-12-08
影响因子：
15
通讯作者：
Coughlin, EB
中科院分区：
文献类型：
--
作者：
Ilker, MF;Nüsslein, K;Coughlin, EB
两亲性阳离子聚降冰片烯衍生物可溶于水，由模块化降冰片烯单体制备而成，具有较宽的分子量范围（M-n = 1600-137 500 g/mol）和较窄的多分散性（PDI = 1.1-1.3）。测量并比较通过生长抑制测定测定的抗菌活性和针对人红细胞的溶血活性，以确定聚合物相对于哺乳动物细胞对细菌的选择性。测定了单体重复单元疏水性和聚合物分子量对抗菌和溶血活性的影响。据观察，重复单元的疏水性对抗菌和溶血活性具有显着影响。通过测量聚合物诱导的染料从大单层囊泡中的渗漏，证实了聚合物的脂质膜破坏活性。通过模块化降冰片烯衍生物的无规共聚来调节聚合物的整体疏水性，获得了高选择性、非溶血性抗菌活性。对于适当的单体组合物，针对细菌与人红细胞的选择性经确定超过 100。
Amphiphilic cationic polynorbomene derivatives, soluble in water, were prepared from modular norbomene monomers, with a wide range of molecular weights (M-n = 1600-137 500 g/mol) and narrow polydispersities (PDI = 1.1-1.3). The antibacterial activity determined by growth inhibition assays and the hemolytic activity against human red blood cells were measured and compared to determine the selectivity of the polymers for bacterial over mammalian cells. The effects of monomer repeat unit hydrophobicity and polymer molecular weight on antibacterial and hemolytic activities were determined. The hydrophobicity of the repeat unit was observed to have dramatic effects on antibacterial and hemolytic activities. Lipid membrane disruption activities of the polymers was confirmed by measuring polymer-induced dye leakage from large unilamellar vesicles. By tuning the overall hydrophobicity of the polymer through random copolymerizations of modular norbomene derivatives, highly selective, nonhemolytic antibacterial activities were obtained. For appropriate monomer composition, selectivity against bacteria versus human red blood cells was determined to be over 100.