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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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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. |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Funding Information: | Funder Grant number UNSPECIFIED BB/M011151/1 |
Depositing User: | Pure (York) |
Date Deposited: | 28 Feb 2019 15:00 |
Last Modified: | 08 Feb 2025 00:33 |
Published Version: | https://doi.org/10.1021/jacs.9b00056 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1021/jacs.9b00056 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:143112 |
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