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
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: |
|
||||||
Depositing User: | Pure (York) | ||||||
Date Deposited: | 02 Nov 2020 16:10 | ||||||
Last Modified: | 06 Dec 2023 13:57 | ||||||
Published Version: | https://doi.org/10.3390/molecules25174025 | ||||||
Status: | Published | ||||||
Refereed: | Yes | ||||||
Identification Number: | https://doi.org/10.3390/molecules25174025 | ||||||
Related URLs: |