PDF(Pubmed)
Abstract：
Muraymycins are a subclass of antimicrobially active uridine-derived natural products. Biological data on several muraymycin analogues have been reported, including some inhibitory in vitro activities toward their target protein, the bacterial membrane enzyme MraY. However, a structure-activity relationship (SAR) study on naturally occurring muraymycins based on such in vitro data has been missing so far. In this work, we report a detailed SAR investigation on representatives of the four muraymycin subgroups A-D using a fluorescence-based in vitro MraY assay. For some muraymycins, inhibition of MraY with IC50 values in the low-picomolar range was observed. These inhibitory potencies were compared with antibacterial activities and were correlated to modelling data derived from a previously reported X-ray crystal structure of MraY in complex with a muraymycin inhibitor. Overall, these results will pave the way for the development of muraymycin analogues with optimized properties as antibacterial drug candidates.
摘要：
Muraymycins是具有抗菌活性的尿苷衍生的天然产物的亚类。已经报道了几种穆雷霉素类似物的生物学数据，包括对其靶蛋白的一些体外抑制活性，细菌膜酶MraY。然而,迄今为止，基于此类体外数据的天然存在的muraymycins的结构-活性关系（SAR）研究一直缺失。在这项工作中,我们报告了使用基于荧光的体外MraY测定法对四个Muraymycin亚群A-D的代表进行的详细SAR调查。对于一些muraymycins,观察到MraY的抑制,IC50值在低皮摩尔范围内.将这些抑制效力与抗菌活性进行了比较，并将其与先前报道的MraY与muraymycin抑制剂复合的X射线晶体结构得出的建模数据相关联。总的来说,这些结果将为开发具有优化特性的穆雷霉素类似物作为抗菌候选药物铺平道路。
