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dc.contributor.authorKlein, Raphael
dc.contributor.authorCendron, Laura
dc.contributor.authorMontanari, Maria
dc.contributor.authorBellio, Pierangelo
dc.contributor.authorCelenza, Giuseppe
dc.contributor.authorMaso, Lorenzo
dc.contributor.authorTondi, Donatella
dc.contributor.authorBrenk, Ruth
dc.date.accessioned2021-06-24T06:03:48Z
dc.date.available2021-06-24T06:03:48Z
dc.date.created2021-02-15T13:07:36Z
dc.date.issued2020
dc.identifier.issn2218-273X
dc.identifier.urihttps://hdl.handle.net/11250/2760978
dc.description.abstractThe worldwide spread of β-lactamases able to hydrolyze last resort carbapenems contributes to the antibiotic resistance problem and menaces the successful antimicrobial treatment of clinically relevant pathogens. Class A carbapenemases include members of the KPC and GES families. While drugs against KPC-type carbapenemases have recently been approved, for GES-type enzymes, no inhibitors have yet been introduced in therapy. Thus, GES carbapenemases represent important drug targets. Here, we present an in silico screening against the most prevalent GES carbapenemase, GES-5, using a lead-like compound library of commercially available compounds. The most promising candidates were selected for in vitro validation in biochemical assays against recombinant GES-5 leading to four derivatives active as high micromolar competitive inhibitors. For the best inhibitors, the ability to inhibit KPC-2 was also evaluated. The discovered inhibitors constitute promising starting points for hit to lead optimization.en_US
dc.language.isoengen_US
dc.publisherMDPIen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleTargeting the Class A Carbapenemase GES-5 via Virtual Screeningen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2020 by the authors.en_US
dc.source.articlenumber304en_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.doi10.3390/biom10020304
dc.identifier.cristin1889883
dc.source.journalBiomoleculesen_US
dc.relation.projectNotur/NorStore: NN9376Ken_US
dc.identifier.citationBiomolecules. 2020, 10 (2), 304.en_US
dc.source.volume10en_US
dc.source.issue2en_US


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