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dc.contributor.authorde Munnik, Mariskaen
dc.contributor.authorLohans, Christopher T.en
dc.contributor.authorLangley, Gareth W.en
dc.contributor.authorBon, Corentinen
dc.contributor.authorBrem, Jürgenen
dc.contributor.authorSchofield, Christopher J.en
dc.date.accessioned2019-11-25T15:07:31Z
dc.date.available2019-11-25T15:07:31Z
dc.date.issued2019
dc.identifier.urihttp://hdl.handle.net/1974/27461
dc.description.abstractMycobacterium tuberculosis l,d‐transpeptidases (Ldts), which are involved in cell‐wall biosynthesis, have emerged as promising targets for the treatment of tuberculosis. However, an efficient method for testing inhibition of these enzymes is not currently available. We present a fluorescence‐based assay for LdtMt2, which is suitable for high‐throughput screening. Two fluorogenic probes were identified that release a fluorophore upon reaction with LdtMt2, thus making it possible to assess the availability of the catalytic site in the presence of inhibitors. The assay was applied to a panel of β‐lactam antibiotics and related inhibitors; the results validate observations that the (carba)penem subclass of β‐lactams are more potent Ldt inhibitors than other β‐lactam classes, though unexpected variations in potency were observed. The method will enable systematic structure–activity relationship studies on Ldts, thereby facilitating the identification of new antibiotics active against M. tuberculosis.en
dc.language.isoenen
dc.publisherWileyen
dc.rightsThis is the peer reviewed version of the following article: de Munnik et a. A Fluorescence‐Based Assay for Screening β‐Lactams Targeting the Mycobacterium tuberculosis Transpeptidase LdtMt2, which has been published in final form at https://doi.org/10.1002/cbic.201900379. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.en
dc.subjectAntibioticsen
dc.subjectBeta-Lactamsen
dc.subjectFluorescent Probesen
dc.subjectInhibitorsen
dc.subjectTuberculosisen
dc.titleA Fluorescence‐Based Assay for Screening β‐Lactams Targeting the Mycobacterium tuberculosis Transpeptidase LdtMt2en
dc.typepreprinten
dc.identifier.doihttps://doi.org/10.1002/cbic.201900379


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