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 against Staphylococcus aureus, Acinetobacter baumannii, and Enterococcus faecalis prior 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.

中文翻译：

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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。

抗生素抗性细菌感染的流行日益增长，因此需要新型抗菌剂，可以从组合文库中快速鉴定出抗菌剂。我们报告使用类肽库琼脂扩散（PLAD）分析来筛选针对ESKAPE病原体的类肽库，包括优化每种病原体的分析条件。通过对类肽亲脂性与抗菌效力和哺乳动物细胞毒性之间的关系的详细研究，本文介绍的工作重点在于组合类肽库设计的定制。然后使用上述筛选方法应用从该优化中收集到的信息，以检查类肽库对金黄色葡萄球菌，鲍曼不动杆菌，和粪肠球菌在用长烷基尾官能化之前和之后。数据表明，类肽的整体疏水性而不是简单的烷基尾长与哺乳动物细胞毒性密切相关。此外，这项工作证明了PLAD分析在快速评估相似文库中分子特性变化的影响方面的实用性。