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RESEARCH PRODUCT
Picomolar inhibition of cholera toxin by a pentavalent ganglioside GM1os-calix[5]arene
Alessandro CasnatiC.a.g.m. WeijersSilvia BernardiHan ZuilhofHan ZuilhofFrancesco SansoneJaime Garcia-hartjesTom WennekesMichel Gilbertsubject
Models MolecularCholera ToxinbindingStereochemistrydesignCalix[5]areneEpithelial cellsG(M1) GangliosideHeat-labile enterotoxinmedicine.disease_causeligandBiochemistrycrystalMultivalency effectsCholeraCausative agentsmedicinePotencyHumansoligosaccharidePhysical and Theoretical ChemistryIC50Vibrio choleraeheat-labile enterotoxinVLAGchemistry.chemical_classificationgm1 mimicsGangliosideInhibition assaysChemistryCholera toxinOrganic ChemistryOligosaccharideBinding domainLigand (biochemistry)ValenciesOrganische ChemiehexamethylenetetramineChemistryPositive ionsaffinityAntitoxinsCalixarenesrecognitionBinding domaindescription
Cholera toxin (CT), the causative agent of cholera, displays a pentavalent binding domain that targets the oligosaccharide of ganglioside GM1 (GM1os) on the periphery of human abdominal epithelial cells. Here, we report the first GM1os-based CT inhibitor that matches the valency of the CT binding domain (CTB). This pentavalent inhibitor contains five GM1os moieties linked to a calix[5]arene scaffold. When evaluated by an inhibition assay, it achieved a picomolar inhibition potency (IC50 = 450 pM) for CTB. This represents a significant multivalency effect, with a relative inhibitory potency of 100000 compared to a monovalent GM1os derivative, making GM1os-calix[5]arene one of the most potent known CTB inhibitors. This journal is © The Royal Society of Chemistry 2013.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2013-05-22 |