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 calixarene 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-calixarene one of the most potent known CTB inhibitors.
- heat-labile enterotoxin
- gm1 mimics
Garcia-Hartjes, J., Bernardi, S., Weijers, C. A. G. M., Wennekes, T., Gilbert, M., Sansone, F., ... Zuilhof, H. (2013). Picomolar inhibition of cholera toxin by a pentavalent ganglioside GM1os-calixarene. Organic & Biomolecular Chemistry, 11, 4340-4349. https://doi.org/10.1039/c3ob40515j