The role of hydrophobicity in the antimicrobial and hemolytic activities of polymethacrylate derivatives.
The role of hydrophobicity in the antimicrobial and hemolytic activities of polymethacrylate derivatives.
复制标题
DOI：
10.1002/chem.200801523
复制
发表时间：
2009
影响因子：
4.3
通讯作者：
DeGrado, William F.
中科院分区：
文献类型：
--
作者：
Kuroda, Kenichi;Caputo, Gregory A.;DeGrado, William F.
我们通过自由基共聚的甲基丙烯酸酯单体与阳离子或疏水基团，合成了阳离子无规两亲性共聚物，并评价了它们的抗菌和溶血活性。疏水基团的性质，和聚合物的组成和长度进行了系统的变化，以研究结构参数如何影响聚合物的活性。这使我们能够获得适合用作无毒抗菌剂以及非选择性聚合物杀生物剂的聚合物的最佳组合物。抗微生物活性与疏水基团的摩尔分数（fHB）呈S形关系。溶血活性随着fHB的增加而增加，并在fHB的高值下趋于稳定，特别是对于高分子量聚合物。对于每个聚合物系列，HC 50值与聚合物链中疏水侧链的数量的曲线在双对数曲线中显示出良好的相关性和线性关系。我们还开发了一个理论模型来分析聚合物的溶血活性，并证明了溶血活性可以描述为通过将疏水侧链分配到脂质层和聚合物链的疏水性塌陷来平衡聚合物的膜结合。对染料标记的聚合物与大的单层囊泡的膜结合的研究表明，聚合物的疏水性增强了它们与脂质双层的结合，并诱导溶液中聚合物链的塌陷，降低了聚合物对膜的表观亲和力。
We synthesized cationic random amphiphilic copolymers by radical copolymerization of methacrylate monomers with cationic or hydrophobic groups and evaluated their antimicrobial and hemolytic activities. The nature of the hydrophobic groups, and polymer composition and length were systematically varied to investigate how structural parameters affect polymer activity. This allowed us to obtain the optimal composition of polymers suitable to act as non-toxic antimicrobials as well as non-selective polymeric biocides. The antimicrobial activity depends sigmoidally on the mole fraction of hydrophobic groups (fHB). The hemolytic activity increases as fHB increases and levels off at high values of fHB, especially for the high-molecular-weight polymers. Plots of HC50 values versus the number of hydrophobic side chains in a polymer chain for each polymer series showed a good correlation and linear relationship in the log–log plots. We also developed a theoretical model to analyze the hemolytic activity of polymers and demonstrated that the hemolytic activity can be described as a balance of membrane binding of polymers through partitioning of hydrophobic side chains into lipid layers and the hydrophobic collapsing of polymer chains. The study on the membrane binding of dye-labeled polymers to large, unilamellar vesicles showed that the hydrophobicity of polymers enhances their binding to lipid bilayers and induces collapse of the polymer chain in solution, reducing the apparent affinity of polymers for the membranes.
登录
查看更多内容
影响因子：
15
作者：
Ilker, MF;Nüsslein, K;Coughlin, EB
通讯作者：
Coughlin, EB
影响因子：
2.9
作者：
Caputo, GA;London, E
通讯作者：
London, E
影响因子：
3.4
作者：
Kaiser, RD;London, E
通讯作者：
London, E
影响因子：
3
作者：
Chen, Y;Worley, SD;Williams, JF
通讯作者：
Williams, JF
影响因子：
15
作者：
Hamuro, Y;Schneider, JP;DeGrado, WF
通讯作者：
DeGrado, WF