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Chem Biol. 2010 Nov 24;17(11):1250-5. doi: 10.1016/j.chembiol.2010.09.014.

Cell-penetrant, nanomolar O-GlcNAcase inhibitors selective against lysosomal hexosaminidases.

Author information

1
Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee DD15EH, Scotland.

Abstract

Posttranslational modification of metazoan nucleocytoplasmic proteins with N-acetylglucosamine (O-GlcNAc) is essential, dynamic, and inducible and can compete with protein phosphorylation in signal transduction. Inhibitors of O-GlcNAcase, the enzyme removing O-GlcNAc, are useful tools for studying the role of O-GlcNAc in a range of cellular processes. We report the discovery of nanomolar OGA inhibitors that are up to 900,000-fold selective over the related lysosomal hexosaminidases. When applied at nanomolar concentrations on live cells, these cell-penetrant molecules shift the O-GlcNAc equilibrium toward hyper-O-GlcNAcylation with EC₅₀ values down to 3 nM and are thus invaluable tools for the study of O-GlcNAc cell biology.

PMID:
21095575
PMCID:
PMC3032886
DOI:
10.1016/j.chembiol.2010.09.014
[Indexed for MEDLINE]
Free PMC Article

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