Main > INFECTIOUS DISEASES > Cholera > Toxins. > EnteroToxins. > EnteroToxin PentaValent Inhibitor > Org.: USA. U (Research) > NPLS Contents

---

A group led by AUTHORS designed a multivalent inhibitor for another bacterial toxin--an enterotoxin related to cholera toxin. When ingested, the enterotoxin s five identical binding sites recognize and bind to ganglioside carbohydrate groups in the gut lining.

Designing a multivalent ligand capable of inhibiting enterotoxin was not easy because the toxin s binding sites are widely separated. AUTHORS solved this problem by designing "octopus" ligands that have five arms--that is, pentavalent ligands with long linkers that extend five carbohydrate-binding galactose "fingers" out toward the toxin binding sites. The best pentavalent ligand had submicromolar affinity for the toxin--a level of potency 105 times higher than that of the corresponding monovalent ligand.

"We have not sought commercial development for our compounds so far," AUTHORS tells , "primarily because we want to make much better ligands before we put them into practical use." Because of the ligands modular design, "we can independently optimize any module and incorporate it into a new ligand with enhanced affinity toward enterotoxin," AUTHOR says. "Right now, we are focusing on designing better finger modules. We have in hand easily synthesizable fingers that are 100 to 1,000 times better than the one we described in our original paper. We are very optimistic that we will soon be able to synthesize pentavalent ligands against enterotoxin with dissociation constants [down to the] picomolar range. At that time, we will initiate commercial development of our compounds."




NPLS Contents's products
This section has no products