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 ganglios ide GM1, Gal beta 1-3CGalNAc 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 radiolabele d toxin, finding was obtained, although substantially reduced, with th e amide and to a lesser extent with the benzylamide and also the C(1)- alcohol. In the assay system used, the methyl-, ethyl-, or propylamide s 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 ag reement with the recently published crystal structure of the B-subunit in complex with the GM1 pentasaccharide.