Schröder, Sybrin P, Wu, Liang orcid.org/0000-0003-0294-7065, Artola, Marta et al. (9 more authors) (2018) Gluco-1 H-imidazole : A New Class of Azole-Type β-Glucosidase Inhibitor. Journal of the American Chemical Society. pp. 1-4. ISSN 1520-5126
Abstract
Gluco-azoles competitively inhibit glucosidases by transition-state mimicry and their ability to interact with catalytic acid residues in glucosidase active sites. We noted that no azole-type inhibitors described, to date, possess a protic nitrogen characteristic for 1 H-imidazoles. Here, we present gluco-1 H-imidazole, a gluco-azole bearing a 1 H-imidazole fused to a glucopyranose-configured cyclitol core, and three close analogues as new glucosidase inhibitors. All compounds inhibit human retaining β-glucosidase, GBA1, with the most potent ones inhibiting this enzyme (deficient in Gaucher disease) on a par with glucoimidazole. None inhibit glucosylceramide synthase, cytosolic β-glucosidase GBA2 or α-glucosidase GAA. Structural, physical and computational studies provide first insights into the binding mode of this conceptually new class of retaining β-glucosidase inhibitors.
Metadata
Authors/Creators: |
|
||||
---|---|---|---|---|---|
Copyright, Publisher and Additional Information: | © 2018 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. | ||||
Keywords: | Journal Article | ||||
Dates: |
|
||||
Institution: | The University of York | ||||
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) | ||||
Funding Information: |
|
||||
Depositing User: | Pure (York) | ||||
Date Deposited: | 17 Apr 2018 11:10 | ||||
Last Modified: | 06 Dec 2023 12:25 | ||||
Published Version: | https://doi.org/10.1021/jacs.8b02399 | ||||
Status: | Published | ||||
Refereed: | Yes | ||||
Identification Number: | https://doi.org/10.1021/jacs.8b02399 |
Download
Filename: Schroder_imidazole_revised_1_.pdf
Description: Schroder_imidazole_revised(1)