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