Viuff Agnete, Salamone Stéphane, McLoughlin Joseph, Deane Janet E, Jensen Henrik H
Department of Chemistry, Aarhus University, Langelandsgade 140, 8000 Aarhus C, Denmark.
Department of Clinical Neuroscience, Cambridge Institute of Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, U.K.
ACS Med Chem Lett. 2020 Dec 18;12(1):56-59. doi: 10.1021/acsmedchemlett.0c00377. eCollection 2021 Jan 14.
Competitive inhibitors of galactocerebrosidase (GALC) could be candidates for pharmacological chaperone therapy of patients with Krabbe disease. The known and selective nortropane-type iminosugar -noeurostegine has been found to competitively inhibit GALC with = 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 -noeurostegine binds to the active site of GALC in its bicyclic form.
半乳糖脑苷脂酶（GALC）的竞争性抑制剂可能是用于克拉伯病患者药理伴侣疗法的候选药物。已发现已知的选择性降托烷型亚氨基糖——神经鞘氨醇在pH 4.6时以Ki = 7 μM的浓度竞争性抑制GALC，其效力比类似的脱氧神经鞘氨醇高330倍。通过X射线蛋白质晶体学表明，神经鞘氨醇以其二环形式结合到GALC的活性位点。
