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Galactooligosaccharides (GOS) inhibit Vibrio cholerae toxin binding to its GM1 receptor

Sinclair, H.R., de Slegte, J., Gibson, G.R. and Rastall, R.A. (2009) Galactooligosaccharides (GOS) inhibit Vibrio cholerae toxin binding to its GM1 receptor. Journal of Agricultural and Food Chemistry, 57 (8). pp. 3113-3119. ISSN 0021-8561

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To link to this article DOI: 10.1021/jf8034786

Abstract/Summary

It is widely reported that cholera toxin (Ctx) remains a significant cause of gastrointestinal disease globally, particularly in developing countries where access to clean drinking water is at a premium. Vaccines are prohibitively expensive and have shown only short-term protection. Consequently, there is scope for continued development of novel treatment strategies. One example is the use of galactooligosaccharides (GOS) as functional mimics for the cell-surface toxin receptor (GM1). In this study, GOS fractions were fractionated using cation exchange chromatography followed by structural characterization using a combination of hydrophilic interaction liquid chromatography (HILIC) and electrospray ionization mass spectrometry (ESI-MS) such that their molecular weight profiles were known. Each profile was correlated against biological activity measured using a competitive inhibitory GM1-linked ELISA. GOS fractions containing > 5% hexasaccharides (DP6) exhibited > 90% binding, with EC50 values between 29.27 and 56.04 mg/mL. Inhibition by GOS DP6, was dose dependent, with an EC50 value of 5.10 mg/mL (5.15 mu M MW of 990 Da). In removing low molecular weight carbohydrates that do possess prebiotic, nutraceutical, and/or biological properties and concentrating GOS DP5 and/or DP6, Ctx antiadhesive activity per unit of (dry) weight was improved. This could be advantageous in the manufacture of pharmaceutical or nutraceutical formulations for the treatment or prevention of an acute or chronic disease associated with or caused by the adhesion and/or uptake of a Ctx or HLT.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences
ID Code:12986
Uncontrolled Keywords:Mass spectrometry, HILIC, galactooligosaccharide, antiadhesive, Vibrio cholerae toxin, glycomimetic , HYDROPHILIC-INTERACTION CHROMATOGRAPHY, HEAT-LABILE ENTEROTOXIN, ESCHERICHIA-COLI, MASS-SPECTROMETRY, HUMAN-MILK, CRYSTAL-STRUCTURE, OLIGOSACCHARIDES, GANGLIOSIDE, CELLS, ADHESION

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