Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/1275
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dc.contributor.authorSampathkumar, Srinivasa-Gopalan-
dc.contributor.authorNeelamegham, Sriram-
dc.contributor.authorWang, Shuen-Shiuan-
dc.contributor.authorSolar, Virginia Del-
dc.contributor.authorYu, Xinheng-
dc.contributor.authorAntonopoulos, Aristotelis-
dc.contributor.authorFriedman, Alan E-
dc.contributor.authorAgarwal, Kavita-
dc.contributor.authorGarg, Monika-
dc.contributor.authorAhmed, Syed Meheboob-
dc.contributor.authorAddhya, Ahana-
dc.contributor.authorNasirikenari, Mehrab-
dc.contributor.authorLau, Joseph T-
dc.contributor.authorDell, Anne-
dc.contributor.authorHaslam, Stuart M-
dc.date.accessioned2022-02-07T05:35:02Z-
dc.date.available2022-02-07T05:35:02Z-
dc.date.issued2021-05-
dc.identifier.urihttp://hdl.handle.net/123456789/1275-
dc.description.abstractThere is a critical need to develop small-molecule inhibitors of mucin-type O-linked glycosylation. The best-known reagent currently is benzyl-GalNAc, but it is effective only at millimolar concentrations. This article demonstrates that Ac5GalNTGc, a peracetylated C-2 sulfhydryl-substituted GalNAc, fulfills this unmet need. When added to cultured leukocytes, breast cells, and prostate cells, Ac5GalNTGc increased cell-surface VVA binding by ∼10-fold, indicating truncation of O-glycan biosynthesis. Cytometry, mass spectrometry, and western blot analysis of HL-60 promyelocytes demonstrated that 50-80 μM Ac5GalNTGc prevented elaboration of 30%-60% of the O-glycans beyond the Tn-antigen (GalNAcα1-Ser/Thr) stage. The effect of the compound on N-glycans and glycosphingolipids was small. Glycan inhibition induced by Ac5GalNTGc resulted in 50%-80% reduction in leukocyte sialyl-Lewis X expression and L-/P-selectin-mediated rolling under flow conditions. Ac5GalNTGc was pharmacologically active in mouse. It reduced neutrophil infiltration to sites of inflammation by ∼60%. Overall, Ac5GalNTGc may find diverse applications as a potent inhibitor of O-glycosylationen_US
dc.language.isoenen_US
dc.publisherElsevier Ltden_US
dc.subjectO-glycan; cell adhesion; glycosylation; inflammation; inhibitor; mucin; neutrophil; selectin; sialyl-Lewis X; small moleculeen_US
dc.titleEfficient inhibition of O-glycan biosynthesis using the hexosamine analog Ac5GalNTGcen_US
dc.typeArticleen_US
dc.journalCell Chem Biolen_US
dc.volumeno28en_US
dc.issueno5en_US
dc.pages699-710.e5en_US
Appears in Collections:Chemical Glycobiology, Publications

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