Carbohydrate-based anti-adhesive inhibition of Vibrio cholerae toxin binding to GM1-OS immobilized into artificial planar lipid membranes.
We have studied 'food grade' sialyloligosaccharides (SOS) as anti-adhesive drugs or receptor analogues, since the terminal sialic acid residue has already been shown to contribute significantly to the adhesion and pathogenesis of the Vibrio cholerae toxin (Ctx). GM1-oligosaccharide (GM1-OS) was immobilized into a supporting POPC lipid bilayer onto a surface plasmon resonance (SPR) chip, and the interaction between uninhibited Ctx and GM1-OS-POPC was measured. SOS inhibited 94.7% of the Ctx binding to GM1-OS-POPC at 10mg/mL. The SOS EC(50) value of 5.521mg/mL is high compared with 0.2811microg/mL (182.5rhoM or 1.825x10(-10)M) for GM1-OS. The commercially available sialyloligosaccharide (SOS) mixture Sunsial E((R)) is impure, containing one monosialylated and two disialylated oligosaccharides in the ratio 9.6%, 6.5% and 17.5%, respectively, and 66.4% protein. However, these inexpensive food-grade molecules are derived from egg yolk and could be used to fortify conventional food additives, by way of emulsifiers, sweeteners and/or preservatives. The work further supports our hypothesis that SOS could be a promising natural anti-adhesive glycomimetic against Ctx and prevent subsequent onset of disease.
Sinclair
Haydn R
HR
University of Reading, Whiteknights, United Kingdom.
Kemp
Fred
F
Slegte
Jaap de
Jd
Gibson
Glenn R
GR
Rastall
Robert A
RA
D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000737:chemistry*; D002772:Cholera Toxin / Q000737:chemistry / Q000378:metabolism*; D008567:Membranes, Artificial; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D020349:Surface Plasmon Resonance
D002241:Carbohydrates; D008567:Membranes, Artificial; D009844:Oligosaccharides; C016735:sialooligosaccharides; C037563:G(M1)-oligosaccharide; D002772:Cholera Toxin