硝基集团作为共价酶抑制中的掩蔽亲电试剂。
The Nitro Group as a Masked Electrophile in Covalent Enzyme Inhibition.
机构信息
Department of Chemistry , University at Buffalo , Buffalo , New York 14260-3000 , United States.
Hauptman-Woodward Institute and Department of Structural Biology, Jacobs School of Medicine and Biomedical Sciences , University at Buffalo , Buffalo , New York 14203-1102 , United States.
出版信息
ACS Chem Biol. 2018 Jun 15;13(6):1470-1473. doi: 10.1021/acschembio.8b00225. Epub 2018 May 23.
Abstract
We report the unprecedented reaction between a nitroalkane and an active-site cysteine residue to yield a thiohydroximate adduct. Structural and kinetic evidence suggests the nitro group is activated by conversion to its nitronic acid tautomer within the active site. The nitro group, therefore, shows promise as a masked electrophile in the design of covalent inhibitors targeting binding pockets with appropriately placed cysteine and general acid residues.
摘要
我们报告了一种前所未有的硝基烷与活性中心半胱氨酸残基之间的反应，生成了硫代羟氨加合物。结构和动力学证据表明，硝基在活性中心内转化为其亚硝酮互变异构体而被激活。因此，硝基有望成为设计针对具有适当位置半胱氨酸和广义酸残基的结合口袋的共价抑制剂的掩蔽亲电试剂。
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