Cationic Amphiphiles with Specificity against Gram-Positive and Gram-Negative Bacteria: Chemical Composition and Architecture Combat Bacterial Membranes
Cationic Amphiphiles with Specificity against Gram-Positive and Gram-Negative Bacteria: Chemical Composition and Architecture Combat Bacterial Membranes
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DOI：
10.1021/acs.langmuir.9b00110
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发表时间：
2019-04-23
期刊：
影响因子：
3.9
通讯作者：
Uhrich, Kathryn E.
中科院分区：
文献类型：
--
作者：
Moretti, Alysha;Weeks, Richard M.;Uhrich, Kathryn E.
小分子阳离子两亲体（CAms）被设计用来对抗耐药性细菌的快速增长。cam的设计目标是破坏细菌膜的结构完整性，导致细胞破裂和死亡。cam的离散结构特征多种多样，进行结构-活性关系研究以指导合理设计具有理想选择性和细胞相容性的有效抗菌素。特别地，评价了阳离子构象柔韧性、疏水畴柔韧性和疏水畴结构的影响。确定了它们对革兰氏阳性和革兰氏阴性细菌的抗菌效果的影响，并通过评估它们对哺乳动物细胞的影响建立了它们的安全性概况。所有CAms都具有抗细菌的活性，疏水结构域的刚性和分支结构有助于特异性。从该项目中获得的见解将有助于凸轮结构的优化。
Small-molecule cationic amphiphiles (CAms) were designed to combat the rapid rise in drug-resistant bacteria. CAms were designed to target and compromise the structural integrity of bacteria membranes, leading to cell rupture and death. Discrete structural features of CAms were varied, and structure-activity relationship studies were performed to guide the rational design of potent antimicrobials with desirable selectivity and cytocompatibility profiles. In particular, the effects of cationic conformational flexibility, hydrophobic domain flexibility, and hydrophobic domain architecture were evaluated. Their influence on antimicrobial efficacy in Gram-positive and Gram-negative bacteria was determined, and their safety profiles were established by assessing their impact on mammalian cells. All CAms have a potent activity against bacteria, and hydrophobic domain rigidity and branched architecture contribute to specificity. The insights gained from this project will aid in the optimization of CAm structures.