EVIDENCE OF CONFORMATIONAL HETEROGENEITY FOR CARBOHYDRATE MIMETICS - NMR-STUDY OF METHYL BETA-C-LACTOSIDE IN AQUEOUS-SOLUTION

The structure and internal dynamics of methyl beta-C-lactoside in aque ous solution has been derived by H-1 NMR and molecular modeling. A sim ulated annealing procedure under nuclear Overhauser effect (nOe) restr aints produced a family of 50 structures. However, no single one of th em was satisfactory; for each a rather important deviation between exp erimental and simulated data was found. Examination of the H-H correla tion times given by off-resonance ROESY and comparison of the experime ntal and simulated coupling constants related to the interglycosidic d ihedral angles indicated that the problem arose from internal mobility around the psi angle. Using the result of a phi/psi map, we have trie d to find the best agreement between experimental and back-calculated nOe distances with two families having the same angle phi but differen t psi values. The best fit is obtained for 40% of (phi(A) = 295 degree s; psi(A) = 300 degrees) and 60% of (phi(B) = 295 degrees; psi(B) = 13 0 degrees). This result represents the first step toward comparison of the structure and dynamics of C- and O-glycosides in aqueous solution .