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.
Original language | English |
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Pages (from-to) | 4340-4349 |
Journal | Organic & Biomolecular Chemistry |
Volume | 11 |
DOIs | |
Publication status | Published - 2013 |
Keywords
- heat-labile enterotoxin
- gm1 mimics
- binding
- ligand
- hexamethylenetetramine
- oligosaccharide
- recognition
- affinity
- crystal
- design