Evaluating the Effect of Peptoid Lipophilicity on Antimicrobial Potency, Cytotoxicity, and Combinatorial Library Design.
Evaluating the Effect of Peptoid Lipophilicity on Antimicrobial Potency, Cytotoxicity, and Combinatorial Library Design.
复制标题
评估类肽亲脂性对抗菌效力、细胞毒性和组合文库设计的影响。
DOI：
10.1021/acscombsci.7b00007
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发表时间：
2017
影响因子：
--
通讯作者：
Bicker,KevinL
中科院分区：
文献类型：
--
作者：
Turkett,JeremyA;Bicker,KevinL
抗生素耐药细菌感染的日益普遍需要新型抗菌药物，这些抗菌药物可以从组合库中快速识别。我们报告使用的类肽库琼脂扩散（PLAD）测定筛选类肽库对ESKAPE病原体，包括每种病原体的测定条件的优化。这里介绍的工作重点是通过详细研究类肽的亲脂性如何与抗菌效力和哺乳动物细胞毒性相关来定制组合类肽库设计。然后使用上述筛选方法应用从该优化中收集的信息，以检查在用长烷基尾官能化之前和之后类肽文库对金黄色葡萄球菌、鲍氏不动杆菌和粪肠球菌的相对效力。数据表明，总体类肽疏水性而不仅仅是烷基尾长与哺乳动物细胞毒性强烈相关。此外，这项工作证明了PLAD测定在快速评估类似文库中分子性质变化的影响中的实用性。
Growing prevalence of antibiotic resistant bacterial infections necessitates novel antimicrobials, which could be rapidly identified from combinatorial libraries. We report the use of the peptoid library agar diffusion (PLAD) assay to screen peptoid libraries against the ESKAPE pathogens, including the optimization of assay conditions for each pathogen. Work presented here focuses on the tailoring of combinatorial peptoid library design through a detailed study of how peptoid lipophilicity relates to antibacterial potency and mammalian cell toxicity. The information gleaned from this optimization was then applied using the aforementioned screening method to examine the relative potency of peptoid libraries againstStaphylococcus aureus,Acinetobacter baumannii, andEnterococcus faecalisprior to and following functionalization with long alkyl tails. The data indicate that overall peptoid hydrophobicity and not simply alkyl tail length is strongly correlated with mammalian cell toxicity. Furthermore, this work demonstrates the utility of the PLAD assay in rapidly evaluating the effect of molecular property changes in similar libraries.