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Sialyloligosaccharides inhibit cholera toxin binding to the GM1 receptor

Sinclair, H.R., Smejkal, C.W., Glister, C., Kemp, F., van den Heuvel, E., de Slegte, J., Gibson, G.R. and Rastall, R.A. (2008) Sialyloligosaccharides inhibit cholera toxin binding to the GM1 receptor. Carbohydrate Research, 343 (15). pp. 2589-2594. ISSN 0008-6215

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To link to this article DOI: 10.1016/j.carres.2008.07.008

Abstract/Summary

It is recognised that cholera toxin (Ctx) is a significant cause of gastrointestinal disease globally, particularly in developing countries where access to uncontaminated drinking water is at a premium. Ctx vaccines are prohibitively expensive and only give short-term protection. Consequently, there is scope for the development of alternative control strategies or prophylactics. This may include the use of oligosaccharides as functional mimics for the cell-surface toxin receptor (GM I). Furthermore, the sialic acid component of epithelial receptors has already been shown to contribute significantly to the adhesion and pathogenesis of Ctx. Here, we demonstrate the total inhibition of Ctx using GM1-competitive ELISA with 25 mg mL(-1) of a commercial preparation of sialyloligosaccharides (SOS). The IC50 value was calculated as 5.21 mg mL(-1). One-hundred percent inhibition was also observed at all concentrations of Ctx-HRP tested with 500 ng mL(-1) GM1-OS. Whilst SOS has much lower affinity for Ctx than GM1-OS, the commercial preparation is impure containing only 33.6% carbohydrate; however, the biantennary nature of SOS appears to give a significant increase in potency over constituent monosaccahride residues. It is proposed that SOS could be used as a conventional food additive, such as in emulsifiers, stabilisers or sweeteners, and are classified as nondigestible oligosaccharides that pass into the small intestine, which is the site of Ctx pathogenesis. (C) 2008 Elsevier Ltd. All rights reserved.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences
Faculty of Life Sciences > School of Biological Sciences > Biomedical Sciences
Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences
ID Code:12984
Uncontrolled Keywords:Antiadhesive, Sialyloligosaccharides, Biantennary, Vibrio cholerae toxin, Receptor-analogue, Glycomimetics , HEAT-LABILE ENTEROTOXIN, VACCINE CVD 103-HGR, ESCHERICHIA-COLI, VIBRIO-CHOLERAE, GANGLIOSIDE GM1, EGG-YOLK, HUMAN-MILK, CRYSTAL-STRUCTURE, SIALIC-ACID, OLIGOSACCHARIDES INHIBIT

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