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

Autor: Viuff A; Department of Chemistry, Aarhus University, Langelandsgade 140, 8000 Aarhus C, Denmark., Salamone S; Department of Chemistry, Aarhus University, Langelandsgade 140, 8000 Aarhus C, Denmark., McLoughlin J; Department of Clinical Neuroscience, Cambridge Institute of Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, U.K., Deane JE; Department of Clinical Neuroscience, Cambridge Institute of Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, U.K., Jensen HH; Department of Chemistry, Aarhus University, Langelandsgade 140, 8000 Aarhus C, Denmark.
Jazyk: angličtina
Zdroj: ACS medicinal chemistry letters [ACS Med Chem Lett] 2020 Dec 18; Vol. 12 (1), pp. 56-59. Date of Electronic Publication: 2020 Dec 18 (Print Publication: 2021).
DOI: 10.1021/acsmedchemlett.0c00377
Abstrakt: 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.
Competing Interests: The authors declare no competing financial interest.
(© 2020 American Chemical Society.)
Databáze: MEDLINE
Externí odkaz: