INVOLVEMENT OF THE GLUCOSE MOIETY IN THE MOLECULAR RECOGNITION OF METHYL BETA-LACTOSIDE BY RICIN - SYNTHESIS, CONFORMATIONAL-ANALYSIS, AND BINDING-STUDIES OF DIFFERENT DERIVATIVES AT THE C-3 REGION

Syntheses of the 3-aminodeoxy (4), 3-deoxy-3-methyl (5), and 3-epi (6) derivatives of methyl beta-lactoside (1) have been achieved from 1 in a straightforward way, and their solution conformations in water and dimethyl sulfoxide analysed through molecular mechanics and dynamics c alculations and nuclear magnetic resonance data. The overall shape of all the compounds studied is fairly similar and may be described by co nformers included in a low energy region with Phi = 15 +/- 45 degrees and Psi = -25 +/- 30 degrees, that is ca. 5% of the total potential en ergy surface for the glycosidic linkages of the disaccharides. The bin ding of the different compounds to ricin, the galactose-specific toxin from Ricinus communis, has been investigated. The results confirm the involvement of the C-3 region in a nonpolar interaction with the prot ein at the periphery of the combining site.