title: O-GlcNAc transferase inhibitors: current tools and future challenges.
abstract: The O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification (O-GlcNAcylation) is the dynamic and reversible attachment of N-acetylglucosamine to serine and threonine residues of nucleocytoplasmic target proteins. It is abundant in metazoa, involving hundreds of proteins linked to a plethora of biological functions with implications in human diseases. The process is catalysed by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) that add and remove sugar moieties respectively. OGT knockout is embryonic lethal in a range of animal models, hampering the study of the biological role of O-GlcNAc and the dissection of catalytic compared with non-catalytic roles of OGT. Therefore, selective and potent chemical tools are necessary to inhibit OGT activity in the context of biological systems. The present review focuses on the available OGT inhibitors and summarizes advantages, limitations and future challenges.
authors: Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
authors: Riccardo
authors: R
authors: Trapannone
authors: Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
authors: Karim
authors: K
authors: Rafie
authors: Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K. Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K. d.m.f.vanaalten@dundee.ac.uk.
authors: Daan M F
authors: DM
authors: van Aalten
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D057166:High-Throughput Screening Assays; D006801:Humans; D008958:Models, Molecular; D017351:N-Acetylglucosaminyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013379:Substrate Specificity / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase
keywords: O-linked N-acetylglucosamine (O-GlcNAc); O-linked N-acetylglucosamine (O-GlcNAc) transferase; inhibitor; post-translational modification; protein structure; signal transduction