Reidl Cory T, Heath Tahirah K, Darwish Iman, Torrez Rachel M, Moore Maxwell, Gild Elliot, Nocek Boguslaw P, Starus Anna, Holz Richard C, Becker Daniel P
Department of Chemistry and Biochemistry, Loyola University Chicago, 1032 West Sheridan Road, Chicago, IL 60660, USA.
Department of Chemistry, Department of Molecular Biosciences, Chemistry of Life Processes Institute, Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, IL 60208-3113, USA.
Antibiotics (Basel). 2020 Sep 11;9(9):595. doi: 10.3390/antibiotics9090595.
Inhibitors of the bacterial enzyme dapE-encoded -succinyl-L,L-diaminopimelic acid desuccinylase (DapE; EC 3.5.1.18) hold promise as antibiotics with a new mechanism of action. Herein we describe the discovery of a new series of indoline sulfonamide DapE inhibitors from a high-throughput screen and the synthesis of a series of analogs. Inhibitory potency was measured by a ninhydrin-based DapE assay recently developed by our group. Molecular docking experiments suggest active site binding with the sulfonamide acting as a zinc-binding group (ZBG).
细菌酶dapE编码的琥珀酰-L,L-二氨基庚二酸去琥珀酰化酶（DapE；EC 3.5.1.18）抑制剂有望成为具有新作用机制的抗生素。在此，我们描述了通过高通量筛选发现的一系列新的吲哚啉磺酰胺DapE抑制剂以及一系列类似物的合成。抑制效力通过我们小组最近开发的基于茚三酮的DapE测定法进行测量。分子对接实验表明，活性位点结合时磺酰胺作为锌结合基团（ZBG）起作用。
