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dc.contributor.authorLiu, Ta-wei
dc.contributor.authorZandberg, Wesley F.
dc.contributor.authorGloster, Tracey M.
dc.contributor.authorDeng, Lehua
dc.contributor.authorMurray, Kelsey D
dc.contributor.authorShan, Xiaoyang
dc.contributor.authorVocadlo, David Jaro
dc.date.accessioned2018-10-12T11:30:06Z
dc.date.available2018-10-12T11:30:06Z
dc.date.issued2018-06-25
dc.identifier.citationLiu , T , Zandberg , W F , Gloster , T M , Deng , L , Murray , K D , Shan , X & Vocadlo , D J 2018 , ' Metabolic inhibitors of O -GlcNAc transferase (OGT) that act in vivo implicate decreased O -GlcNAc levels in leptin-mediated nutrient sensing ' , Angewandte Chemie International Edition , vol. 57 , no. 26 , pp. 7644-7648 . https://doi.org/10.1002/anie.201803254en
dc.identifier.issn1433-7851
dc.identifier.otherPURE: 253087741
dc.identifier.otherPURE UUID: 6ec7b15e-ca85-4797-ae73-4bdec7c5c82c
dc.identifier.othercrossref: 10.1002/anie.201803254
dc.identifier.otherScopus: 85047492974
dc.identifier.otherWOS: 000435766800007
dc.identifier.urihttp://hdl.handle.net/10023/16199
dc.descriptionThis work was supported by a grant from the Natural Sciences and Engineering Research Council of Canada (NSERC). D.J.V. is a scholar of the Michael Smith Foundation of Health Research (MSFHR) and a Tier II Canada Research Chair in Chemical Glycobiology. T.M.G. was supported by a Sir Henry Wellcome postdoctoral fellowship (WT082572) and a Research Career Development Fellowship from the Wellcome Trust (WT095828).en
dc.description.abstractO‐linked glycosylation of serine and threonine residues of nucleocytoplasmic proteins with N‐acetylglucosamine (O‐GlcNAc) residues is catalyzed by O‐GlcNAc transferase (OGT). O‐GlcNAc is conserved within mammals and is implicated in a wide range of physiological processes. Here we describe metabolic precursor inhibitors of OGT suitable for use both in cells and in vivo in mice. These 5‐thiosugar analogues of N‐acetylglucosamine are assimilated through a convergent metabolic pathway, most likely involving N‐acetylglucosamine‐6‐phosphate de‐N‐acetylase (NAGA) to generate a common OGT inhibitor within cells. Of these inhibitors, we show that 2‐deoxy‐2‐N‐hexanamide‐5‐thio‐D‐glucopyranoside (5SGlcNHex) acts in vivo to induce dose‐ and time‐dependent decreases in O‐GlcNAc levels in various tissues. Decreased O‐GlcNAc correlates, both in vitro within adipocytes and in vivo within mice, with lower levels of transcription factor Sp1 and the satiety‐inducing hormone leptin ‐ revealing a link between decreased O‐GlcNAc levels and nutrient sensing in peripheral tissues of mammals.
dc.language.isoeng
dc.relation.ispartofAngewandte Chemie International Editionen
dc.rights© 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.en
dc.subjectGlycoproteinen
dc.subjectThiosugaren
dc.subjectNucleotide sugarsen
dc.subjectLeptinen
dc.subjectNutrient sensingen
dc.subjectQD Chemistryen
dc.subjectNDASen
dc.subject.lccQDen
dc.titleMetabolic inhibitors of O-GlcNAc transferase (OGT) that act in vivo implicate decreased O-GlcNAc levels in leptin-mediated nutrient sensingen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1002/anie.201803254
dc.description.statusPeer revieweden
dc.identifier.urlhttps://europepmc.org/articles/PMC6055616en


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