title: Inhibitors of bacterial N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) and demonstration of in vitro antimicrobial activity.
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.
authors.affiliation: Department of Chemistry, Loyola University, 6525 North Sheridan Road, Chicago, IL 60626, USA.
authors.forename: Danuta
authors.initials: D
authors.lastname: Gillner
authors.forename: Nicola
authors.initials: N
authors.lastname: Armoush
authors.forename: Richard C
authors.initials: RC
authors.lastname: Holz
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Becker
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001665:Binding Sites; D003960:Diaminopimelic Acid / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D016297:Mutagenesis, Site-Directed; D013379:Substrate Specificity
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D003960:Diaminopimelic Acid; D000581:Amidohydrolases