CONFORMATIONAL-ANALYSIS OF THE CARBOHYDRATE PORTION OF T AND TN HAPTENS BY NMR-SPECTROSCOPY AND MOLECULAR MODELING

The conformations of the crotyl derivatives of the T (beta-D-Gal(1-->3 )-Crotylalpha-D-GalNAc) and T(N) (Crotylalpha-D-GalNAc) haptens as wel l as of Mebeta-D-Gal were investigated in D2O, DMSO-d6 and 85% H2O: 15 % acetone-d6 using H-1 and C-13 NMR spectroscopy and molecular modelin g. The two sugar moieties are in a C-4(1) conformation and they adopt a quasi-parallel orientation in the T hapten, with hydrogens H1' and H 3 being in close proximity. The hydroxymethyl chains adopt a gt confor mation, the NH and H2 are antiperiplanar whereas the crotyl chain disp lays significant segmental mobility. Vicinal coupling constants of hyd roxyl protons and saturation transfer rates in aqueous media indicate that the hydroxyl groups are relatively mobile except for OH2' which p robably forms a weak hydrogen bond with the amide nitrogen. An energy- minimized molecular model consistent with all the NMR data could be co nstructed and areas favorable to hydrophilic interactions could be det ermined. Except for the rotamer distribution of the hydroxymethyl grou p, the conformations are very similar in all three solvents.