Artola, Marta, Kuo, Chi-Lin, Lelieveld, Lindsey T. et al. (7 more authors) (2019) Functionalized cyclophellitols are selective glucocerebrosidase inhibitors and induce a bona fide neuropathic Gaucher model in zebrafish. Journal of the American Chemical Society. 4214–4218. ISSN 1520-5126
Abstract
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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Copyright, Publisher and Additional Information: | © 2019 American Chemical Society. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details. | ||||
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Institution: | The University of York | ||||
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) | ||||
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Depositing User: | Pure (York) | ||||
Date Deposited: | 28 Feb 2019 15:00 | ||||
Last Modified: | 31 Jan 2024 00:50 | ||||
Published Version: | https://doi.org/10.1021/jacs.9b00056 | ||||
Status: | Published | ||||
Refereed: | Yes | ||||
Identification Number: | https://doi.org/10.1021/jacs.9b00056 | ||||
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