分拣酶
排序酶A
化学
金黄色葡萄球菌
对接(动物)
丙烯腈
共价键
部分
立体化学
半胱氨酸
生物膜
活力测定
生物化学
细菌
酶
细胞
有机化学
聚合物
共聚物
护理部
基因
生物
医学
遗传学
细菌蛋白
作者
Shuwen Lei,Yang Hu,Cheng Yuan,Ran Sun,Juntao Wang,Yong Zhang,Yang Zhang,Dan Lü,Lei Fu,Faqin Jiang
标识
DOI:10.1016/j.ejmech.2021.114032
摘要
Sortase A (SrtA) is a cysteine transpeptidase of most gram-positive bacteria that is responsible for the anchoring of many surface protein virulence factors to the cell wall. SrtA ablation has demonstrated to alleviate the infection without affecting the viability of bacteria. Herein, a series of benzofuran cyanide derivatives were synthesized and evaluated. Several compounds exhibited excellent inhibitory activity against SrtA with IC50 values from 3.3 μM to 21.8 μM compared with the known SrtA inhibitor pHMB (IC50 = 130 μM). Ⅲ-1, Ⅲ-15, Ⅲ-34 and V-1 showed potent inhibitory effects on biofilm formation with IC50 values from 2.1 μM to 54.2 μM. Invasion assays showed the four compounds caused a decrease of 4%-24.0% in the uptake of the S. aureus strain by 293T cells. Further assay showed that compound Ⅲ-15 decreased the amount of cell wall-associated protein A by 26.5%. Structure-activity relationship and docking studies demonstrated that the acrylonitrile moiety of the compounds played an important role in enhancing the activity. When the double bond of acrylonitrile changed to single bond, the activity was decreased significantly. This indicates that acrylonitrile, which is a Michael receptor, can inhibit the activity of SrtA by covalent binding effectively to the thiol group of Cys184.
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