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

doi:10.1002/anie.201507985

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

Résultats de recherche: Contribution à un journal › Article publié dans une revue, révisé par les pairs › Revue par des pairs

45 Citations (Scopus)

Résumé

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.

langue originale	Anglais
Pages (de - à)	15429-15433
Nombre de pages	5
journal	Angewandte Chemie - International Edition
Volume	54
Numéro de publication	51
Les DOIs	https://doi.org/10.1002/anie.201507985
état	Publié - 14 déc. 2015
Modification externe	Oui

Accès au document

10.1002/anie.201507985

Autres fichiers et liens

Lien vers la publication dans Scopus

Empreinte digitale

Voici les principaux termes ou expressions associés à « A Convenient Approach to Stereoisomeric Iminocyclitols: Generation of Potent Brain-Permeable OGA Inhibitors ». Ces libellés thématiques sont générés à partir du titre et du résumé de la publication. Ensemble, ils forment une empreinte digitale unique.

CCDC 1403768: Experimental Crystal Structure Determination
Bergeron-Brlek, M. (Créateur), Goodwin-Tindall, J. (Créateur), Cekic, N. (Créateur), Roth, C. (Créateur), Zandberg, W. F. (Créateur), Shan, X. (Créateur), Varghese, V. (Créateur), Chan, S. (Créateur), Davies, G. J. (Créateur), Vocadlo, D. J. (Créateur) & Britton, R. (Créateur), Cambridge Crystallographic Data Centre, 2016
DOI: 10.5517/cc1j3qv6
Ensemble de données

Contient cette citation

Bergeron-Brlek, M., Goodwin-Tindall, J., Cekic, N., Roth, C., Zandberg, W. F., Shan, X., Varghese, V., Chan, S., Davies, G. J., Vocadlo, D. J., & Britton, R. (2015). A Convenient Approach to Stereoisomeric Iminocyclitols: Generation of Potent Brain-Permeable OGA Inhibitors. Angewandte Chemie - International Edition, 54(51), 15429-15433. https://doi.org/10.1002/anie.201507985

@article{6eaeb12670014063bb41025f082a8ace,

title = "A Convenient Approach to Stereoisomeric Iminocyclitols: Generation of Potent Brain-Permeable OGA Inhibitors",

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.",

keywords = "enzymes, glycosides, heterocycles, hydrolases, inhibitors",

author = "Milan Bergeron-Brlek and Jake Goodwin-Tindall and Nevena Cekic and Christian Roth and Zandberg, \{Wesley F.\} and Xiaoyang Shan and Vimal Varghese and Sherry Chan and Davies, \{Gideon J.\} and Vocadlo, \{David J.\} and Robert Britton",

note = "Publisher Copyright: {\textcopyright} 2015 WILEY-VCH Verlag GmbH \& Co. KGaA, Weinheim.",

year = "2015",

month = dec,

day = "14",

doi = "10.1002/anie.201507985",

language = "English",

volume = "54",

pages = "15429--15433",

journal = "Angewandte Chemie - International Edition",

issn = "1433-7851",

publisher = "John Wiley and Sons Ltd",

number = "51",

}

Bergeron-Brlek, M, Goodwin-Tindall, J, Cekic, N, Roth, C, Zandberg, WF, Shan, X, Varghese, V, Chan, S, Davies, GJ, Vocadlo, DJ & Britton, R 2015, 'A Convenient Approach to Stereoisomeric Iminocyclitols: Generation of Potent Brain-Permeable OGA Inhibitors', Angewandte Chemie - International Edition, VOL. 54, Numéro 51, p. 15429-15433. https://doi.org/10.1002/anie.201507985

A Convenient Approach to Stereoisomeric Iminocyclitols: Generation of Potent Brain-Permeable OGA Inhibitors. / Bergeron-Brlek, Milan; Goodwin-Tindall, Jake; Cekic, Nevena et al.
Dans: Angewandte Chemie - International Edition, Vol 54, Numéro 51, 14.12.2015, p. 15429-15433.

Résultats de recherche: Contribution à un journal › Article publié dans une revue, révisé par les pairs › Revue par des pairs

TY - JOUR

T1 - A Convenient Approach to Stereoisomeric Iminocyclitols

T2 - Generation of Potent Brain-Permeable OGA Inhibitors

AU - Bergeron-Brlek, Milan

AU - Goodwin-Tindall, Jake

AU - Cekic, Nevena

AU - Roth, Christian

AU - Zandberg, Wesley F.

AU - Shan, Xiaoyang

AU - Varghese, Vimal

AU - Chan, Sherry

AU - Davies, Gideon J.

AU - Vocadlo, David J.

AU - Britton, Robert

PY - 2015/12/14

Y1 - 2015/12/14

N2 - 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.

AB - 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.

KW - enzymes

KW - glycosides

KW - heterocycles

KW - hydrolases

KW - inhibitors

UR - https://www.scopus.com/pages/publications/84955215786

U2 - 10.1002/anie.201507985

DO - 10.1002/anie.201507985

M3 - Journal Article

C2 - 26545827

AN - SCOPUS:84955215786

SN - 1433-7851

VL - 54

SP - 15429

EP - 15433

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

IS - 51

ER -

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

Résumé

Accès au document

Autres fichiers et liens

Empreinte digitale

Ensembles de données

CCDC 1403768: Experimental Crystal Structure Determination

Contient cette citation