By the same authors

From the same journal

From the same journal

A Convenient Approach to Stereoisomeric Iminocyclitols: Generation of Potent Brain-Permeable OGA Inhibitors

Research output: Contribution to journalArticle

Published copy (DOI)

Author(s)

  • 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

Department/unit(s)

Publication details

JournalAngewandte Chemie International Edition
DateE-pub ahead of print - 6 Dec 2015
DatePublished (current) - 14 Dec 2015
Number of pages6
Early online date6/12/15
Original languageEnglish

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.

Bibliographical note

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

    Research areas

  • Enzymes, Glycosides, Heterocycles, Hydrolases, Inhibitors

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