Biscationic Tartaric Acid-Based Amphiphiles: Charge Location Impacts Antimicrobial Activity
Biscationic Tartaric Acid-Based Amphiphiles: Charge Location Impacts Antimicrobial Activity
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DOI：
10.1021/acs.langmuir.5b03347
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发表时间：
2015-11-03
期刊：
影响因子：
3.9
通讯作者：
Uhrich, Kathryn E.
中科院分区：
文献类型：
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作者：
Faig, Allison;Arthur, Timothy D.;Uhrich, Kathryn E.
由于其独特的破坏细菌细胞膜的能力，阳离子两亲体作为抗菌剂受到越来越多的关注。虽然广泛的研究表明，两亲物质的疏水电荷比显著调节抗菌活性，但较少的工作集中在阐明电荷位置对两亲物质生物活性的具体影响。在这项研究中，合成了两个系列的阳离子两亲体，称为bola-like和gemini-like，它们的疏水电荷比相似，但电荷位置不同，并评估了它们的抗菌活性。bola样两亲体对两种革兰氏阳性菌均表现出优先活性，活性随疏水性的增加而增加，而gemini样两亲体对革兰氏阳性菌和革兰氏阴性菌均表现出活性，活性随疏水性的增加而降低。在确定了每一个两亲体系列（双曲线型和双子座型）的先导化合物后，生物物理实验表明这两种两亲体都具有膜活性；值得注意的是，铅类双亲化合物在膜相互作用中表现出对静电相互作用的强烈依赖。相比之下，铅类bola两亲体表现出对疏水和静电贡献的依赖。这些结果表明，电荷位置显著影响阳离子两亲体的抗菌和膜活性。
Cationic amphiphiles have received increasing attention as antimicrobials given their unique ability to disrupt bacteria cell membranes. While extensive research has demonstrated that amphiphiles' hydrophobic-to-charge ratio significantly modulates antibacterial activity, less work has focused on elucidating the specific impact of charge location on amphiphile bioactivity. In this study, two series of cationic amphiphiles, termed bola-like and gemini-like, were synthesized with analogous hydrophobic-to-charge ratios yet differing charge location, and their resulting antibacterial activity was assessed. Bola-like amphiphiles exhibited preferential activity against two Gram-positive bacteria, with activity increasing with increasing hydrophobicity, whereas gemini-like amphiphiles were active against both Gram-positive and Gram-negative bacteria, with activity decreasing with increasing hydrophobicity. After identifying lead compounds from each amphiphile series (bola- and gemini-like), biophysical experiments indicated that both amphiphiles were membrane-active; notably, the lead gemini-like amphiphile exhibited a strong dependence on electrostatic interactions for membrane interaction. In contrast, the lead bola-like amphiphile exhibited a reliance on both hydrophobic and electrostatic contributions. These results demonstrate that charge location significantly impacts cationic amphiphiles' antibacterial and membrane activity.