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.
Picomolar inhibition of cholera toxin by pentavalent ganglioside GM1os-calix[5]arene / J., Garcia Hartjes; Bernardi, Silvia; C. A. G. M., Weijers; T., Wennekes; Sansone, Francesco; Casnati, Alessandro; H., Zuilhof. - In: ORGANIC & BIOMOLECULAR CHEMISTRY. - ISSN 1477-0520. - 11:(2013), pp. 4340-4349. [10.1039/C3OB40515J]
Picomolar inhibition of cholera toxin by pentavalent ganglioside GM1os-calix[5]arene
BERNARDI, Silvia;SANSONE, Francesco;CASNATI, Alessandro;
2013-01-01
Abstract
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.File | Dimensione | Formato | |
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