Probing the acceptor substrate binding site of Trypanosoma cruzi trans-sialidase with systematically modified substrates and glycoside libraries
(2011) In Organic and Biomolecular Chemistry 9(5). p.1653-1660- 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 alpha-(2 -> 3)-sialylation of non-reducing terminal beta-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... (More)
- 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 alpha-(2 -> 3)-sialylation of non-reducing terminal beta-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. (Less)
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https://lup.lub.lu.se/record/1868923
- author
- Harrison, Jennifer A. ; Kartha, K. P. Ravindranathan ; Fournier, Eric J. L. ; Lowary, Todd L. ; Malet, Carles ; Nilsson, Ulf LU ; Hindsgaul, Ole ; Schenkman, Sergio ; Naismith, James H. and Field, Robert A.
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Organic and Biomolecular Chemistry
- volume
- 9
- issue
- 5
- pages
- 1653 - 1660
- publisher
- Royal Society of Chemistry
- external identifiers
-
- wos:000287368800049
- scopus:79951621284
- pmid:21253654
- ISSN
- 1477-0539
- DOI
- 10.1039/c0ob00826e
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240)
- id
- ea44a9f6-4af7-459f-af8e-97b1d4ee4162 (old id 1868923)
- date added to LUP
- 2016-04-01 10:09:56
- date last changed
- 2022-04-12 02:39:29
@article{ea44a9f6-4af7-459f-af8e-97b1d4ee4162,
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 alpha-(2 -> 3)-sialylation of non-reducing terminal beta-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.}},
author = {{Harrison, Jennifer A. and Kartha, K. P. Ravindranathan and Fournier, Eric J. L. and Lowary, Todd L. and Malet, Carles and Nilsson, Ulf and Hindsgaul, Ole and Schenkman, Sergio and Naismith, James H. and Field, Robert A.}},
issn = {{1477-0539}},
language = {{eng}},
number = {{5}},
pages = {{1653--1660}},
publisher = {{Royal Society of Chemistry}},
series = {{Organic and Biomolecular Chemistry}},
title = {{Probing the acceptor substrate binding site of Trypanosoma cruzi trans-sialidase with systematically modified substrates and glycoside libraries}},
url = {{http://dx.doi.org/10.1039/c0ob00826e}},
doi = {{10.1039/c0ob00826e}},
volume = {{9}},
year = {{2011}},
}