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

摘要

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.