Title

Inhibitors of Bacterial N-succinyl-L,L-diaminopimelic Acid Desuccinylase (DapE) and Demonstration of in vitro Antimicrobial Activity

Document Type

Article

Publication Date

11-15-2009

Source Publication

Bioorganic & Medicinal Chemistry Letters

Source ISSN

0960-894x

Abstract

The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) is a critical bacterial enzyme for the construction of the bacterial cell wall. A screen biased toward compounds containing zinc-binding groups (ZBG’s) including thiols, carboxylic acids, boronic acids, phosphonates and hydroxamates has delivered a number of micromolar inhibitors of DapE from Haemophilus influenzae, including the low micromolar inhibitor L-captopril (IC50 = 3.3 μM, Ki = 1.8 μM). In vitro antimicrobial activity was demonstrated for l-captopril against Escherichia coli.

Comments

Bioorganic & Medicinal Chemistry Letters, Vol. 19, No. 22 (November 15, 2009): 6350-6352. DOI.

Richard C. Holz was affiliated with Loyola University-Chicago at the time of publication.