5abf

Publication Abstract from PubMed

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.

A Convenient Approach to Stereoisomeric Iminocyclitols: Generation of Potent Brain-Permeable OGA Inhibitors.,Bergeron-Brlek M, Goodwin-Tindall J, Cekic N, Roth C, Zandberg WF, Shan X, Varghese V, Chan S, Davies GJ, Vocadlo DJ, Britton R Angew Chem Int Ed Engl. 2015 Nov 6. doi: 10.1002/anie.201507985. PMID:26545827^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.