Department of Pharmaceutical Sciences, University of Illinois at Chicago, 833 S. Wood Street, Chicago, Illinois 60612, United States.
Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood Street, Chicago, Illinois 60612, United States.
J Nat Prod. 2020 Mar 27;83(3):657-667. doi: 10.1021/acs.jnatprod.9b01095. Epub 2020 Feb 7.
This study represents a systematic chemical and biological study of the rufomycin (RUF) class of cyclic heptapeptides, which our anti-TB drug discovery efforts have identified as potentially promising anti-TB agents that newly target the caseinolytic protein C1, ClpC1. Eight new RUF analogues, rufomycins NBZ1-NBZ8 (-), as well as five known peptides (-) were isolated and characterized from the strain MJM3502. Advanced Marfey's and X-ray crystallographic analysis led to the assignment of the absolute configuration of the RUFs. Several isolates exhibited potent activity against both pathogens H37Rv and , paired with favorable selectivity (selectivity index >60), which collectively underscores the promise of the rufomycins as potential anti-TB drug leads.
本研究代表了对 rufomycin（RUF）类环七肽的系统化学和生物学研究，我们的抗结核药物发现工作已经确定这些环七肽类化合物作为具有潜在应用前景的抗结核药物，它们可以靶向新型的酪蛋白水解蛋白 C1（ClpC1）。从 菌株 MJM3502 中分离并鉴定了八种新的 RUF 类似物（-）和五种已知肽（-）。高级 Marfey's 和 X 射线晶体学分析导致了 RUFs 的绝对构型的确定。一些分离物对两种病原体 H37Rv 和 均表现出很强的活性，并且具有良好的选择性（选择性指数 >60），这共同凸显了 rufomycins 作为潜在抗结核药物先导化合物的前景。
