Decoupling the Functional Roles of Cationic and Hydrophobic Groups in the Antimicrobial and Hemolytic Activities of Methacrylate Random Copolymers,Biomacromolecules

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Decoupling the Functional Roles of Cationic and Hydrophobic Groups in the Antimicrobial and Hemolytic Activities of Methacrylate Random Copolymers
Biomacromolecules ( IF 5.5 ) Pub Date : 2018-10-15 00:00:00 , DOI: 10.1021/acs.biomac.8b01256
Hamid Mortazavian ₁ , Leanna L Foster ₂ , Rajani Bhat ₁ , Shyrie Patel ₁ , Kenichi Kuroda _{1,

2}

Affiliation

In this study, we report the antimicrobial and hemolytic activities of ternary statistical methacrylate copolymers consisting of cationic ammonium (amino-ethyl methacrylate: AEMA), hydrophobic alkyl (ethyl methacrylate: EMA), and neutral hydroxyl (hydroxyethyl methacrylate: HEMA) side chain monomers. The cationic and hydrophobic functionalities of copolymers mimic the cationic amphiphilicity of naturally occurring antimicrobial peptides (AMPs). The HEMA monomer units were used to separately modulate the compositions of cationic and hydrophobic monomers, and we investigated the effect of each component on the antimicrobial and hemolytic activities of copolymers. Our data indicated that increasing the number of cationic groups of the copolymers to be more than 30 mol % did not increase their antimicrobial activity against Escherichia coli. The number of cationic side chains in a polymer chain at this threshold is 5.5–7.7, which is comparable to those of natural antimicrobial peptides such as maginin (+6). The MIC values of copolymers with >30 mol % of AEMA depend on only the mol % of EMA, indicating that the hydrophobic interactions of the copolymers with E. coli cell membranes determine the antimicrobial activity of copolymers. These results suggest that the roles of cationic and hydrophobic groups can be controlled independently by design in the ternary copolymers studied here.

中文翻译：

解耦甲基丙烯酸酯无规共聚物抗菌和溶血活性中阳离子和疏水基团的功能作用

在这项研究中，我们报告了由阳离子铵（甲基丙烯酸氨基乙酯：AEMA）、疏水烷基（甲基丙烯酸乙酯：EMA）和中性羟基（甲基丙烯酸羟乙酯：HEMA）侧链单体组成的三元统计甲基丙烯酸酯共聚物的抗菌和溶血活性。共聚物的阳离子和疏水官能团模仿天然存在的抗菌肽（AMP）的阳离子两亲性。 HEMA单体单元用于分别调节阳离子和疏水单体的组成，并研究了每种组分对共聚物抗菌和溶血活性的影响。我们的数据表明，将共聚物的阳离子基团数量增加到30 mol%以上并不会增加其对大肠杆菌的抗菌活性。在此阈值下，聚合物链中的阳离子侧链数量为 5.5–7.7，与天然抗菌肽（如马吉宁 (+6)）的数量相当。含有 >30 mol% AEMA 的共聚物的 MIC 值仅取决于 EMA 的 mol%，表明共聚物与大肠杆菌细胞膜的疏水相互作用决定了共聚物的抗菌活性。这些结果表明，在本文研究的三元共聚物中，阳离子基团和疏水基团的作用可以通过设计独立控制。

更新日期：2018-10-15

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