Show simple item record

dc.contributor.authorUddin, Md Jalal
dc.contributor.authorOverkleeft, Hermen S.
dc.contributor.authorLentz, Christian Stephan
dc.date.accessioned2023-11-21T09:43:14Z
dc.date.available2023-11-21T09:43:14Z
dc.date.issued2023-08-08
dc.description.abstractActivity-based protein profiling is a powerful chemoproteomic technique to detect active enzymes and identify targets and off-targets of drugs. Here, we report the use of carmofur- and activity-based probes to identify biologically relevant enzymes in the bacterial pathogen Staphylococcus aureus. Carmofur is an anti-neoplastic prodrug of 5-fluorouracil and also has antimicrobial and anti-biofilm activity. Carmofur probes were originally designed to target human acid ceramidase, a member of the NTN hydrolase family with an active-site cysteine nucleophile. Here, we first profiled the targets of a fluorescent carmofur probe in live S. aureus under biofilm-promoting conditions and in liquid culture, before proceeding to target identification by liquid chromatography/mass spectrometry. Treatment with a carmofur-biotin probe led to enrichment of 20 enzymes from diverse families awaiting further characterization, including the NTN hydrolase-related IMP cyclohydrolase PurH. However, the probe preferentially labeled serine hydrolases, thus displaying a reactivity profile similar to that of carbamates. Our results suggest that the electrophilic N-carbamoyl-5-fluorouracil scaffold could potentially be optimized to achieve selectivity towards diverse enzyme families. The observed promiscuous reactivity profile suggests that the clinical use of carmofur presumably leads to inactivation of a number human and microbial enzymes, which could lead to side effects and/or contribute to therapeutic efficacyen_US
dc.identifier.citationUddin, Overkleeft, Lentz. Activity-Based Protein Profiling in Methicillin-Resistant Staphylococcus aureus Reveals the Broad Reactivity of a Carmofur-Derived Probe. ChemBioChem. 2023en_US
dc.identifier.cristinIDFRIDAID 2185937
dc.identifier.doi10.1002/cbic.202300473
dc.identifier.issn1439-4227
dc.identifier.issn1439-7633
dc.identifier.urihttps://hdl.handle.net/10037/31831
dc.language.isoengen_US
dc.publisherWileyen_US
dc.relation.journalChemBioChem
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2023 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleActivity-Based Protein Profiling in Methicillin-Resistant Staphylococcus aureus Reveals the Broad Reactivity of a Carmofur-Derived Probeen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


File(s) in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record

Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)