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The bicyclic form of galacto-noeurostegine is a potent inhibitor of β-galactocerebrosidase

DOI: 10.1021/acsmedchemlett.0c00377 DOI Help

Authors: Agnete Viuff (Aarhus University) , Stéphane Salamone (Aarhus University) , Joseph Mcloughlin (University of Cambridge) , Janet E. Deane (University of Cambridge) , Henrik H. Jensen (Aarhus University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acs Medicinal Chemistry Letters

State: Published (Approved)
Published: December 2020
Diamond Proposal Number(s): 11235

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 Ki = 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.

Journal Keywords: Krabbe disease; pharmacological chaperone therapy; protein crystal structure; GALC

Diamond Keywords: Krabbe Disease

Subject Areas: Biology and Bio-materials, Chemistry, Medicine

Instruments: I04-Macromolecular Crystallography

Added On: 03/01/2021 10:38

Discipline Tags:

Neurodegenerative Diseases Non-Communicable Diseases Health & Wellbeing Biochemistry Neurology Chemistry Structural biology Organic Chemistry Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)