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ID: ALA4118110
Journal: Bioorg Med Chem Lett
Title: The identification of inhibitory compounds of Rickettsia prowazekii methionine aminopeptidase for antibacterial applications.
Authors: Helgren TR, Seven ES, Chen C, Edwards TE, Staker BL, Abendroth J, Myler PJ, Horn JR, Hagen TJ.
Abstract: Methionine aminopeptidase (MetAP) is a dinuclear metalloprotease responsible for the cleavage of methionine initiator residues from nascent proteins. MetAP activity is necessary for bacterial proliferation and is therefore a projected novel antibacterial target. A compound library consisting of 294 members containing metal-binding functional groups was screened against Rickettsia prowazekii MetAP to determine potential inhibitory motifs. The compounds were first screened against the target at a concentration of 10 µM and potential hits were determined to be those exhibiting greater than 50% inhibition of enzymatic activity. These hit compounds were then rescreened against the target in 8-point dose-response curves and 11 compounds were found to inhibit enzymatic activity with IC50 values of less than 10 µM. Finally, compounds (1-5) were docked against RpMetAP with AutoDock to determine potential binding mechanisms and the results were compared with crystal structures deposited within the PDB.
CiteXplore: 29551481