A Pentavalent Neo Glycoprotein Inhibits Cholera Toxin B Subunit.
Preventing toxins from entering cells by inhibiting their multivalent adhesion to glycolipids in the cell membrane is a strategic route followed by many research groups. In the case of cholera toxin, several engineered glycomolecular assemblies have already shown the value that multivalency can bring to improve the inhibition potency. Several templates to which proper glycan moieties are grafted have been considered ; some of them proved to be effective inhibitors. Nevertheless the applicability of such assemblies as inhibitors is hampered by the difficulty in chemical synthesis and subsequent large scale preparations.
An alternative route followed by the authors of the article is to use a protein scaffold (derived from an inactive mutant to the protein to inhibit) that can be adequately modified with glycan (GM1 in the present case). The size specific modification of the protein scaffold, which is perfectly matched, both in size and valency, to the target protein results in the strongest inhibition potency for the target reported thus far. Since such protein based inhibitors are relatively easy to synthesize their offer attractive applications as biopharmaceutical compounds.