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de Andrade, Peterson, Ahmadipour, Sanaz and Field, Robert A. 
ORCID: https://orcid.org/0000-0001-8574-0275
(2022)
Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase.
Beilstein Journal of Organic Chemistry, 18.
pp. 208-216.
ISSN 1860-5397
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Abstract
Sialic acid is the natural substrate for sialidases and its chemical modification has been a useful approach to generate potent and selective inhibitors. Aiming at advancing the discovery of selective Trypanosoma cruzi trans-sialidase (TcTS) inhibitors, we have synthesised a small series of anomeric 1,2,3-triazole-linked sialic acid derivatives in good yields and high purity via copper-catalysed azide–alkyne cycloaddition (CuAAC, click chemistry) and evaluated their activity towards TcTS and neuraminidase. Surprisingly, the compounds showed practically no TcTS inhibition, whereas ca. 70% inhibition was observed for neuraminidase in relation to the analogues bearing hydrophobic substituents and ca. 5% for more polar substituents. These results suggest that polarity changes are less tolerated by neuraminidase due to the big difference in impact of hydrophobicity upon inhibition, thus indicating a simple approach to differentiate both enzymes. Moreover, such selectivity might be reasoned based on a possible steric hindrance caused by a bulky hydrophobic loop that sits over the TcTS active site and may prevent the hydrophobic inhibitors from binding. The present study is a step forward in exploiting subtle structural differences in sialidases that need to be addressed in order to achieve selective inhibition.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Information: This work was supported by the Flexible Talent Mobility Account (grant BB/S507957/1), funded by the Biotechnology and Biological Sciences Research Council (BBSRC) as part of UK Research and Innovation. This work was also supported by Innovate UK grant 76242: Sugars, Enzymes And Diagnostics (SEAD). |
| Uncontrolled Keywords: | 1,2,3-triazole,inhibition,neuraminidase,sialic acid,trans-sialidase,organic chemistry ,/dk/atira/pure/subjectarea/asjc/1600/1605 |
| Faculty \ School: | Faculty of Science > School of Chemistry, Pharmacy and Pharmacology |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 03 Sep 2024 09:36 |
| Last Modified: | 25 Sep 2024 18:05 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/96463 |
| DOI: | 10.3762/bjoc.18.24 |
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