Ac4GlcNAcF3, an OGT-tolerated but OGA-resistant regulator for O-GlcNAcylation. Issue 6 (15th March 2019)

• Record Type: Journal Article
• 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
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 6(2019)
• Page Start: 802
• Page End: 805
• Publication Date: 2019-03-15
• Subjects: O-GlcNAc transferase -- O-GlcNAcase -- O-GlcNAcylation -- Inhibitors -- Ac4GlcNAcF3; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.01.021
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: O -Linked N-acetylglucosamine ( O -GlcNAc) is an abundant posttranslational monosaccaride-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 (Ac4 GlcNAcF3 ) displayed that Ac4 GlcNAcF3 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 Ac4 GlcNAcF3 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, Ac4 GlcNAcF3 represents a safe and dual regulator for both OGT and OGA, which will benefit the study of O -GlcNAc.