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The Bicyclic Form of galacto-Noeurostegine Is a Potent Inhibitor of β-Galactocerebrosidase.

Accepted version
Peer-reviewed

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Type

Article

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Authors

Viuff, Agnete 
Salamone, Stéphane 
McLoughlin, Joseph 
Deane, Janet E 
Jensen, Henrik H 

Abstract

Competitive inhibitors of galactocerebrosidase (GALC) could be candidates for pharmacological chaperone therapy of patients with Krabbe disease. The known and selective nortropane-type iminosugar galacto-noeurostegine has been found to competitively inhibit GALC with K i = 7 μM at pH 4.6, which is 330-fold more potent than the analogous deoxynoeurostegine. It was shown through X-ray protein crystallography that galacto-noeurostegine binds to the active site of GALC in its bicyclic form.

Description

Keywords

Krabbe disease, pharmacological chaperone therapy, protein crystal structure, GALC

Journal Title

ACS Med Chem Lett

Conference Name

Journal ISSN

1948-5875
1948-5875

Volume Title

12

Publisher

American Chemical Society (ACS)

Rights

All rights reserved
Sponsorship
Royal Society (UF150682)