Self-assembled cationic amphiphiles as antimicrobial peptides mimics: Role of hydrophobicity, linkage type, and assembly state.
Self-assembled cationic amphiphiles as antimicrobial peptides mimics: Role of hydrophobicity, linkage type, and assembly state.
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DOI：
10.1016/j.nano.2016.07.018
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Uhrich KE
中科院分区：
文献类型：
--
作者：
Zhang Y;Algburi A;Wang N;Kholodovych V;Oh DO;Chikindas M;Uhrich KE
受到使用天然抗菌肽(AMPs)治疗耐药细菌感染的巨大希望的启发，阳离子两亲性(CAM)被设计为合成模拟物，以克服相关的限制，包括高制造成本和低代谢稳定性。表面具有两亲性构象的凸轮有望表现出膜溶解特性，从而减少耐药性发展的趋势。通过系统地调节疏水性，优化组成的CAM具有很强的广谱抗菌活性(在低μg/mL范围内具有最低抑菌浓度)，而溶血活性可以忽略不计。电子显微镜图像显示了CaM诱导的细菌膜的形态和超微结构的变化，并验证了其破膜机理。此外，采用全原子分子动力学模拟方法从分子水平上研究了CaM与膜的相互作用。这项研究表明，这些CAM可以作为可行的支架，用于设计下一代AMP模拟物，作为对抗耐药病原体的抗菌替代品。
Inspired by high promise using naturally occurring antimicrobial peptides (AMPs) to treat infections caused by antimicrobial-resistant bacteria, cationic amphiphiles (CAms) were strategically designed as synthetic mimics to overcome associated limitations, including high manufacture cost and low metabolic stability. CAms with facially amphiphilic conformation were expected to demonstrate membrane-lytic properties and thus reduce tendency of resistance development. By systematically tuning the hydrophobicity, CAms with optimized compositions exhibited potent broad-spectrum antimicrobial activity (with minimum inhibitory concentrations in low μg/mL range) as well as negligible hemolytic activity. Electron microscope images revealed the morphological and ultrastructure changes of bacterial membranes induced by CAm treatment and validated their membrane-disrupting mechanism. Additionally, an all-atom molecular dynamics simulation was employed to understand the CAm-membrane interaction on molecular level. This study shows that these CAms can serve as viable scaffolds for designing next generation of AMP mimics as antimicrobial alternatives to combat drug-resistant pathogens.
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影响因子：
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