Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden; Centre for Antibiotic Resistance Research (CARe) at University of Gothenburg, Gothenburg, Sweden.
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
Bioorg Med Chem. 2019 Oct 1;27(19):115043. doi: 10.1016/j.bmc.2019.115043. Epub 2019 Aug 7.
High-throughput screening of small-molecule libraries has led to the identification of thiadiazoles as a new class of inhibitors against Staphylococcus aureus sortase A (SrtA). N-(5-((4-nitrobenzyl)thio)-1,3,4-thiadiazol-2-yl)nicotinamide (IC = 3.8 µM) was identified as a potent inhibitor of SrtA after synthetic modification of hit compounds. Additional ligands developed in this study displayed affinities in the low micromolar range without affecting bacterial growth in vitro. The study also suggest a new mode of action through covalent binding to the active site cysteine.
高通量筛选小分子文库导致噻二唑类化合物被鉴定为一种新型金黄色葡萄球菌表面蛋白 A（SrtA）抑制剂。经过对命中化合物的合成修饰，N-(5-((4-硝基苄基)硫代)-1,3,4-噻二唑-2-基)烟酰胺（IC=3.8µM）被鉴定为一种有效的 SrtA 抑制剂。本研究中开发的其他配体显示出低微摩尔范围内的亲和力，而不会影响体外细菌生长。该研究还通过与活性位点半胱氨酸的共价结合提出了一种新的作用模式。
