Weber, Patrick, Thonhofer, Martin, Averill, Summer et al. (16 more authors) (2020) Mechanistic Insights into the Chaperoning of Human Lysosomal-Galactosidase Activity:Highly Functionalized Aminocyclopentanes and C-5a-Substituted Derivatives of 4-epi-Isofagomine. MOLECULES. 4025. ISSN 1420-3049
Abstract
Glycosidase inhibitors have shown great potential as pharmacological chaperones for lysosomal storage diseases. In light of this, a series of new cyclopentanoid β-galactosidase inhibitors were prepared and their inhibitory and pharmacological chaperoning activities determined and compared with those of lipophilic analogs of the potent β-d-galactosidase inhibitor 4-epi-isofagomine. Structure-activity relationships were investigated by X-ray crystallography as well as by alterations in the cyclopentane moiety such as deoxygenation and replacement by fluorine of a “strategic” hydroxyl group. New compounds have revealed highly promising activities with a range of β-galactosidase-compromised human cell lines and may serve as leads towards new pharmacological chaperones for GM1-gangliosidosis and Morquio B disease.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2020 by the authors. |
Keywords: | 4-epi-isofagomine,Aminocyclopentane,Carbasugar,G-gangliosidosis,Galactosidase inhibitor,Iminoalditol,Pharmacological chaperone |
Dates: |
|
Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Funding Information: | Funder Grant number BBSRC (BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL) BB/R001162/1 THE ROYAL SOCIETY RSRP\R\210004 |
Depositing User: | Pure (York) |
Date Deposited: | 02 Nov 2020 16:10 |
Last Modified: | 17 Dec 2024 00:17 |
Published Version: | https://doi.org/10.3390/molecules25174025 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.3390/molecules25174025 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:167565 |