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Cell-penetrant, nanomolar O-GlcNAcase inhibitors selective against lysosomal hexosaminidasesCell-penetrant, nanomolar O-GlcNAcase inhibitors selective against lysosomal hexosaminidases
Structural highlights
Function[OGA_CLOP1] Biological function unknown. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins. Publication Abstract from PubMedPosttranslational 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 EC values down to 3 nM and are thus invaluable tools for the study of O-GlcNAc cell biology. Cell-penetrant, nanomolar O-GlcNAcase inhibitors selective against lysosomal hexosaminidases.,Dorfmueller HC, Borodkin VS, Schimpl M, Zheng X, Kime R, Read KD, van Aalten DM Chem Biol. 2010 Nov 24;17(11):1250-5. PMID:21095575[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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