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 calculations and nuclear magnetic resonance data. The overall shape of all the compounds studied is fairly similar and may be described by conformers included in a low energy region with phi = 15 +/- 45 degrees and psi = -25 +/- 30 degrees, that is ca. 5% of the total potential energy surface for the glycosidic linkages of the disaccharides. The binding 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 protein at the periphery of the combining site.