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Harrison, Jennifer A., Kartha, K. P. Ravindranathan, Fournier, Eric J. L., Lowary, Todd L., Malet, Carles, Nilsson, Ulf J., Hindsgaul, Ole, Schenkman, Sergio, Naismith, James H. and Field, Robert A. 
ORCID: https://orcid.org/0000-0001-8574-0275
(2011)
Probing the acceptor substrate binding site of Trypanosoma cruzi trans-sialidase with systematically modified substrates and glycoside libraries.
Organic and Biomolecular Chemistry, 9 (5).
pp. 1653-1660.
ISSN 1477-0520
Abstract
Systematically modified octyl galactosides and octyl N-acetyllactosamines were assessed as inhibitors of, and substrates for, T. cruzi trans-sialidase (TcTS) in the context of exploring its acceptor substrate binding site. These studies show that TcTS, which catalyses the α-(2→3)-sialylation of non-reducing terminal β-galactose residues, is largely intolerant of substitution of the galactose 2 and 4 positions whereas substitution of the galactose 6 position is well tolerated. Further studies show that even the addition of a bulky sugar residue (glucose, galactose) does not impact negatively on TcTS binding and turnover, which highlights the potential of 'internal' 6-substituted galactose residues to serve as TcTS acceptor substrates. Results from screening a 93-membered thiogalactoside library highlight a number of structural features (notably imidazoles and indoles) that are worthy of further investigation in the context of TcTS inhibitor development.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | biochemistry,physical and theoretical chemistry,organic chemistry ,/dk/atira/pure/subjectarea/asjc/1300/1303 |
| Faculty \ School: | Faculty of Science > School of Chemistry, Pharmacy and Pharmacology Faculty of Science > School of Biological Sciences |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 06 Sep 2024 13:34 |
| Last Modified: | 25 Sep 2024 18:07 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/96587 |
| DOI: | 10.1039/c0ob00826e |
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