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dc.contributor.authorEspeland, Ludvik Olai
dc.contributor.authorGeorgiou, Charis
dc.contributor.authorKlein, Raphael
dc.contributor.authorBhukya, Hemalatha
dc.contributor.authorHaug, Bengt Erik
dc.contributor.authorUnderhaug, Jarl
dc.contributor.authorMainkar, Prathama S.
dc.contributor.authorBrenk, Ruth
dc.date.accessioned2022-04-04T10:41:59Z
dc.date.available2022-04-04T10:41:59Z
dc.date.created2021-08-12T16:55:46Z
dc.date.issued2021
dc.identifier.issn1860-7179
dc.identifier.urihttps://hdl.handle.net/11250/2989531
dc.description.abstractFabF (3-oxoacyl-[acyl-carrier-protein] synthase 2), which catalyses the rate limiting condensation reaction in the fatty acid synthesis II pathway, is an attractive target for new antibiotics. Here, we focus on FabF from P. aeruginosa (PaFabF) as antibiotics against this pathogen are urgently needed. To facilitate exploration of this target we have set up an experimental toolbox consisting of binding assays using bio-layer interferometry (BLI) as well as saturation transfer difference (STD) and WaterLOGSY NMR in addition to robust conditions for structure determination. The suitability of the toolbox to support structure-based design of FabF inhibitors was demonstrated through the validation of hits obtained from virtual screening. Screening a library of almost 5 million compounds resulted in 6 compounds for which binding into the malonyl-binding site of FabF was shown. For one of the hits, the crystal structure in complex with PaFabF was determined. Based on the obtained binding mode, analogues were designed and synthesised, but affinity could not be improved. This work has laid the foundation for structure-based exploration of PaFabF.en_US
dc.language.isoengen_US
dc.publisherWileyen_US
dc.rightsNavngivelse-Ikkekommersiell 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/deed.no*
dc.titleAn Experimental Toolbox for Structure-Based Hit Discovery for P. aeruginosa FabF, a Promising Target for Antibioticsen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2021 The Authorsen_US
dc.source.articlenumber2715-2726en_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.doi10.1002/cmdc.202100302
dc.identifier.cristin1925674
dc.source.journalChemMedChemen_US
dc.relation.projectNorges forskningsråd: 273588en_US
dc.relation.projectNorges forskningsråd: 245828en_US
dc.relation.projectNorges forskningsråd: 245922en_US
dc.relation.projectNorges forskningsråd: 226244en_US
dc.identifier.citationChemMedChem. 2021, 16 (17), 2715-2726.en_US
dc.source.volume16en_US
dc.source.issue17en_US


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Navngivelse-Ikkekommersiell 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse-Ikkekommersiell 4.0 Internasjonal