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

Authors

Danuta Gillner, Loyola University Chicago
Nicola Armoush, Loyola University Chicago
Richard C. Holz, Marquette University
Daniel P. Becker, Loyola University ChicagoFollow

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, K_i = 1.8 μM). In vitro antimicrobial activity was demonstrated for l-captopril against Escherichia coli.

Comments

Accepted version. Bioorganic & Medicinal Chemistry Letters, Vol. 19, No. 22 (November 15, 2009): 6350-6352. DOI. © 2009 Elsevier Ltd. Used with permission.

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

Recommended Citation

Gillner, Danuta; Armoush, Nicola; Holz, Richard C.; and Becker, Daniel P., "Inhibitors of Bacterial N-succinyl-L,L-diaminopimelic Acid Desuccinylase (DapE) and Demonstration of in vitro Antimicrobial Activity" (2009). Chemistry Faculty Research and Publications. 279.
https://epublications.marquette.edu/chem_fac/279