SELECTIVE-INHIBITION OF N-ACETYLGLUCOSAMINE AND GALACTOSE-SPECIFIC LECTINS INCLUDING THE 14-KDA VERTEBRATE LECTIN BY NOVEL SYNTHETIC BIANTENNARY OLIGOSACCHARIDES

A novel series of synthetic biantennary tri-, penta- and hepta-sacchar ides with terminal 8-GlcNAc, beta-LacNAc and alphaNeuAc(2,6)betaLacNAc residues, respectively, [LacNAc = Galbeta(1,4)GlcNAc] connected to a core Gal residue were evaluated for their inhibitory potencies for spe cific plant and animal lectins. Six isomeric trisaccharides with two b eta-GlcNAc residues at the 2,3-, 2,4-, 2,6-, 3,4-, 3,6-, or 4,6-positi ons of the core Gal were tested for their hemagglutination inhibition activities against two GlcNAc-specific lectins, Griffonia simplicifoli a II (GS II) and wheat germ agglutinin (WGA). The 2,3-, 2,4-, 2,6- and 3,6-trisaccharides inhibited WGA 12-50 times more strongly than GlcNA c, whereas only weak or no inhibition was observed with GS II. The 3,4 - and 4,6-trisaccharides did not inhibit either of the lectins. Six bi antennary isomeric pentasaccharides containing two terminal beta-LacNA c residues with branching patterns similar to the trisaccharides showe d selective hemagglutination inhibition of five Gal/GalNAc-specific pl ant lectins and the 14-kDa Gal-specific calf spleen lectin. The plant lectins include the soybean agglutinin (SBA), ricin agglutinin-I (RCA- 1), and three Erythrina lectins with similar specificities: Erythrina indica (EIL), E. corallodendron (ECorL), and E. cristagalli (ECL). The 2,3-pentasaccharide inhibited only SBA and the 14-kDa lectin, and thu s was a selective inhibitor among the plant lectins. The 2,6-pentasacc haride inhibited SBA, ECL and the 14-kDa lectin, but not RCA-1 or the two other Erythrina lectins. The 4,6-pentasaccharide did not inhibit a ny of the plant lectins, but was a specific inhibitor of the 14-kDa ca lf spleen lectin. Synthetic heptasaccharides analogs with 2,4-, 2,6-, 3,6- and 4,6-branching patterns and terminal alpha(2,6)NeuAc residues all showed 25-fold stronger inhibition against the alpha(2,6)sialic-ac id-specific elderberry (Sambucus nigra L.) bark lectin as compared to a monovalent disaccharide alphaNeuAc(2,6)betaGalOR. The lack of inhibi tion of alphaNeuAc(2,6)betaGalOR derivatives methylated at the C6 of t he Gal residue and a sulfur-linked thiosialoside derivative demonstrat es that the 2,6-anomeric linkage region is important for lectin recogn ition. Selective inhibition of the Gal/GalNAc-specific lectins was obs erved for two isomeric C6 methyl-substituted Gal derivatives of methyl beta-LacNAc which possess different preferred rotamer orientations ab out the C5-C6 bond of the Gal residue.