Probing the acceptor substrate binding site of Trypanosoma cruzi trans-sialidase with systematically modified substrates and glycoside libraries

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. (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

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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:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	06 Sep 2024 13:34
Last Modified:	06 Feb 2025 12:14
URI:	https://ueaeprints.uea.ac.uk/id/eprint/96587
DOI:	10.1039/c0ob00826e

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