1. Inhibitors of bacterial N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) and demonstration of in vitro antimicrobial activity
- Author
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Daniel P. Becker, Danuta Gillner, Richard C. Holz, and Nicola Armoush
- Subjects
Stereochemistry ,Carboxylic acid ,Clinical Biochemistry ,Pharmaceutical Science ,Microbial Sensitivity Tests ,medicine.disease_cause ,Diaminopimelic Acid ,Biochemistry ,Amidohydrolases ,Substrate Specificity ,chemistry.chemical_compound ,Drug Discovery ,medicine ,Escherichia coli ,Amino Acid Sequence ,Enzyme Inhibitors ,Molecular Biology ,chemistry.chemical_classification ,Hydroxamic acid ,Binding Sites ,biology ,Organic Chemistry ,Biological activity ,Antimicrobial ,Haemophilus influenzae ,Anti-Bacterial Agents ,Enzyme ,chemistry ,Enzyme inhibitor ,biology.protein ,Mutagenesis, Site-Directed ,Molecular Medicine ,Diaminopimelic acid - 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 (IC(50)=3.3 microM, K(i)=1.8 microM). In vitro antimicrobial activity was demonstrated for L-captopril against Escherichia coli.
- Published
- 2009