Research output: Contribution to journal › Article › peer-review
Journal | Journal of the American Chemical Society |
---|---|
Date | Accepted/In press - 27 Feb 2019 |
Date | E-pub ahead of print - 27 Feb 2019 |
Date | Published (current) - 13 Mar 2019 |
Issue number | 10 |
Volume | 141 |
Number of pages | 5 |
Pages (from-to) | 4214–4218 |
Early online date | 27/02/19 |
Original language | English |
Gaucher disease is caused by inherited deficiency in glucocerebrosidase (GBA, a retaining β-glucosidase), and deficiency in GBA constitutes the largest known genetic risk factor for Parkinson's disease. In the past, animal models of Gaucher disease have been generated by treatment with the mechanism-based GBA inhibitors, conduritol B epoxide (CBE), and cyclophellitol. Both compounds, however, also target other retaining glycosidases, rendering generation and interpretation of such chemical knockout models complicated. Here we demonstrate that cyclophellitol derivatives carrying a bulky hydrophobic substituent at C8 are potent and selective GBA inhibitors and that an unambiguous Gaucher animal model can be readily generated by treatment of zebrafish with these.
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Project: Research project (funded) › Studentship (central)
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