Ac4GlcNAcF3, an OGT-tolerated but OGA-resistant regulator for O-GlcNAcylation

[Display omitted] O-Linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes. The dynamic nature of O-GlcNAc has enabled researchers to modulate the stoichiometry of O-GlcNAc on proteins...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2019-03, Vol.29 (6), p.802-805
Main Authors: Wang, Haifeng, Guo, Jianshuang, Wang, Nan, Wang, Jiajia, Xue, Qingqing, Wang, Jiyan, Liu, Wenjie, Liu, Kaihui, Cao, Xuefeng, Zhao, Wei, Xi, Rimo, Niu, Youhong, Wang, Peng, Li, Jing
Format: Article
Language:English
Subjects:
Ac4GlcNAcF3
Inhibitors
O-GlcNAc transferase
O-GlcNAcase
O-GlcNAcylation
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Summary:[Display omitted] O-Linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes. The dynamic nature of O-GlcNAc has enabled researchers to modulate the stoichiometry of O-GlcNAc on proteins in order to investigate its function. Cell permeable small moleculars have proven invaluable tools to increase O-GlcNAc levels. Herein, using in vitro substrate screening, we identified GlcNAcF3 as an OGT-accepted but OGA-resistant sugar mimic. Cellular experiments with cell-permeable peracetylated-GlcNAcF3 (Ac4GlcNAcF3) displayed that Ac4GlcNAcF3 was a potent tool to increase O-GlcNAc levels in several cell lines. Further, NIH3T3 cells interfered with OGT (siOGT) showed significant decreasing of O-GlcNAc levels with Ac4GlcNAcF3 treatment, indicating O-GlcNAcF3 was an OGT-dependent modification. In addition, cellular toxic assay confirmed O-GlcNAcF3 production has no significant effect on cell proliferation or viability. Thus, Ac4GlcNAcF3 represents a safe and dual regulator for both OGT and OGA, which will benefit the study of O-GlcNAc.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2019.01.021