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Instruments / Technical Area	Publication Details	Published	Actions
I04-Macromolecular Crystallography	A convenient approach to stereoisomeric iminocyclitols: generation of potent brain-permeable OGA inhibitors Milan Bergeron-Brlek , Jake Goodwin-Tindall , Nevena Cekic , Christian Roth , Wesley F. Zandberg , Xiaoyang Shan , Vimal Varghese , Sherry Chan , Gideon J. Davies , David J. Vocadlo , Robert Britton Angewandte Chemie International Edition DOI: 10.1002/anie.201507985 PMID: 26545827 Diamond Proposal Number(s): [9948] Show Abstract ▼ Abstract: Pyrrolidine-based iminocyclitols are a promising class of glycosidase inhibitors. Reported herein is a convenient epimerization strategy that provides direct access to a range of stereoisomeric iminocyclitol inhibitors of O-GlcNAcase (OGA), the enzyme responsible for catalyzing removal of O-GlcNAc from nucleocytoplasmic proteins. Structural details regarding the binding of these inhibitors to a bacterial homologue of OGA reveal the basis for potency. These compounds are orally available and permeate into rodent brain to increase O-GlcNAc, and should prove useful tools for studying the role of OGA in health and disease.	Nov 2015

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