Syntheses of O-beta-D-galactopyranosyl-(1 leads to 3)-0-(2-acetamido-2-deoxy-alpha(and -beta)-D-galactopyranosyl)-N-tosyl-L-serine and their interaction with D-galactose-binding lectins

Abstract

In order to use, as hapten inhibitors against various galactose-binding lectins, the derivatives of O-beta-D-galactopyranosyl-(1 leads to 3)-O-(2-acetamido-2-deoxy-alpha-D-galactopyranosyl)-L-serine, which is the common core structure of sugar chains of most mucins, the synthesis of these compounds was investigated. Koenigs-Knorr condensation of the 4,6-O-benzylidene derivative of O-(2-acetamido-2-deoxy-alpha-D-galactopyranosyl)-N-tosyl-L-serine methyl ester with 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide gave O-(2,3,4,L-tetra-O-acetyl-beta-D-galactopyranosyl)-(1 leads to 3)-O-(2-acetamido-4,6-O-benzylidene-2-deoxy-alpha-D-galactopyranosyl)-N-tosyl-L-serine. Deacetylation, followed by acid hydrolysis of the benzylidene group, gave O-beta-D-galactopyranosyl-(1 leads to 3)-O-2-acetamido-2-deoxy-alpha-D-galactopyranosyl)-N-tosyl-L-serine. A beta anomer at the glycoside linkage of the 2-acetamido-2-deoxy-D-galactose residue was also synthesized by the same procedure. Agaricus bisporus (mushroom) hemagglutinin was found to recognize the O-alpha-glycosyl linkage between 2-acetamido-2-deoxy-D-galactose and L-serine, in addition to the O-beta-D-galactopyranosyl-(1 leads to 3)-(2-acetamido-2-deoxy-D-galactose sugar sequence, for which Arachis hypogaea (peanut) and Bauhinia purpurea hemagglutinins were found to be specific. Ricinus communis hemagglutinin is more specific for the O-beta-D-galactopyranosyl-(1 leads to 4)-2-acetamido-2-deoxy-D-glucose (commonly found in serum glycoproteins) than for the O-beta-D-galactopyranosyl-(1 linked to 3)-2-acetamido-2-deoxy-D-galactose sequence. With Wistaria floribunda hemagglutinin, not much difference in the inhibitory activities of these two sugar sequences was observed, and O-(2-acetamido-2-deoxy-alpha-D-galactopyranosyl)-N-tosyl-L-serine was the strongest inhibitor against this lectin.