On the role of the carboxyl group of sialic acid in binding of cholera toxin to the receptor glycosphingolipid, GM1.

The carboxyl group of the natural cholera toxin receptor, the ganglioside GM1, Gal beta 1-3GalNAc beta 1-4(NeuAc alpha 2-3)Gal beta 1-4Glc beta 1-Cer, has been converted to a number of C(1)-amides of NeuAc. The binding of cholera toxin B-subunit to these derivatives was monitored by exposing the modified glycolipids, on solid phases, to radiolabeled toxin. Binding was obtained, although substantially reduced, with the amide and to a lesser extent with the benzylamide and also the C(1)-alcohol. In the assay system used, the methyl-, ethyl-, or propylamides did not bind. It was concluded that the hydrogen bonding capacity of a carboxyl or amide group is needed for strong binding. This is in agreement with the recently published crystal structure of the B-subunit in complex with the GM1 pentasaccharide.