Synthetic, conformational, and immunochemical studies of modified Lewis b and Y human blood-group determinants to serve as probes for the combining site of the lectin IV of Griffonia simplicifolia.

Syntheses of the methyl glycosides of the Lewis b [alpha-L-Fuc-(1----2)-beta-D-Gal-(1----3) [alpha-L-Fuc-(1----4)]-beta-D-GlcNAc-] and Y [alpha-L-Fuc-(1----2)-beta-D-Gal-(1----4) [alpha-L-Fuc-(1----3)]-beta-D- GlcNAc-] human blood-group determinants and both their 6a-deoxy and N-deacetylated derivatives are reported. In the case of the Lewis b structure (Leb-OMe), the 6a-O-mesyl and 6a-deoxy-6a-iodo derivatives were also prepared. The conformational preferences predicted by HSEA calculation are shown to be in good agreement with expectations based on 1H- and 13C-n.m.r. spectroscopy. The immunochemical data based on inhibition and thermodynamic studies require that the binding of Leb-OMe and Y-OMe by the lectin IV of Griffonia simplicifolia does not involve recognition of the OMe, NHAc, or 6a-OH group and, consequently, occurs at a cleft at the surface of the protein. The complex formed between the lectin and 6a-deoxy-6a-iodo-Leb-OMe provided the heavy nuclei required for the solution of the X-ray crystal structure.