Lu, Dan, Zhu, Sha, Sobala, Lukasz F. orcid.org/0000-0002-3807-6452 et al. (6 more authors) (2018) From 1,4-Disaccharide to 1,3-Glycosyl Carbasugar:Synthesis of a Bespoke Inhibitor of Family GH99 Endo-α-mannosidase. Organic Letters. pp. 7488-7492. ISSN 1523-7052
Abstract
Understanding the enzyme reaction mechanism can lead to the design of enzyme inhibitors. A Claisen rearrangement was used to allow conversion of an α-1,4-disaccharide into an α-1,3-linked glycosyl carbasugar to target the endo-α-mannosidase from the GH99 glycosidase family, which, unusually, is believed to act through a 1,2-anhydrosugar "epoxide" intermediate. Using NMR and X-ray crystallography, it is shown that glucosyl carbasugar α-aziridines can act as reasonably potent endo-α-mannosidase inhibitors, likely by virtue of their shape mimicry and the interactions of the aziridine nitrogen with the conserved catalytic acid/base of the enzyme active site.
Metadata
Item Type: | Article |
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Authors/Creators: |
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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. |
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 EUROPEAN COMMISSION 322942 |
Depositing User: | Pure (York) |
Date Deposited: | 14 Jan 2019 11:40 |
Last Modified: | 16 Mar 2025 00:07 |
Published Version: | https://doi.org/10.1021/acs.orglett.8b03260 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1021/acs.orglett.8b03260 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:141017 |