The Bicyclic Form of galacto-Noeurostegine Is a Potent Inhibitor of β-Galactocerebrosidase.
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Peer-reviewed
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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.
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Keywords
Krabbe disease, pharmacological chaperone therapy, protein crystal structure, GALC
Journal Title
ACS Med Chem Lett
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Journal ISSN
1948-5875
1948-5875
1948-5875
Volume Title
12
Publisher
American Chemical Society (ACS)
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All rights reserved
Sponsorship
Royal Society (UF150682)