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http://hdl.handle.net/123456789/1275
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DC Field | Value | Language |
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dc.contributor.author | Sampathkumar, Srinivasa-Gopalan | - |
dc.contributor.author | Neelamegham, Sriram | - |
dc.contributor.author | Wang, Shuen-Shiuan | - |
dc.contributor.author | Solar, Virginia Del | - |
dc.contributor.author | Yu, Xinheng | - |
dc.contributor.author | Antonopoulos, Aristotelis | - |
dc.contributor.author | Friedman, Alan E | - |
dc.contributor.author | Agarwal, Kavita | - |
dc.contributor.author | Garg, Monika | - |
dc.contributor.author | Ahmed, Syed Meheboob | - |
dc.contributor.author | Addhya, Ahana | - |
dc.contributor.author | Nasirikenari, Mehrab | - |
dc.contributor.author | Lau, Joseph T | - |
dc.contributor.author | Dell, Anne | - |
dc.contributor.author | Haslam, Stuart M | - |
dc.date.accessioned | 2022-02-07T05:35:02Z | - |
dc.date.available | 2022-02-07T05:35:02Z | - |
dc.date.issued | 2021-05 | - |
dc.identifier.uri | http://hdl.handle.net/123456789/1275 | - |
dc.description.abstract | There 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-glycosylation | en_US |
dc.language.iso | en | en_US |
dc.publisher | Elsevier Ltd | en_US |
dc.subject | O-glycan; cell adhesion; glycosylation; inflammation; inhibitor; mucin; neutrophil; selectin; sialyl-Lewis X; small molecule | en_US |
dc.title | Efficient inhibition of O-glycan biosynthesis using the hexosamine analog Ac5GalNTGc | en_US |
dc.type | Article | en_US |
dc.journal | Cell Chem Biol | en_US |
dc.volumeno | 28 | en_US |
dc.issueno | 5 | en_US |
dc.pages | 699-710.e5 | en_US |
Appears in Collections: | Chemical Glycobiology, Publications |
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File | Description | Size | Format | |
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1-s2.0-S245194562100043X-main.pdf | 4.35 MB | Adobe PDF | View/Open Request a copy |
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