Conformation of the Unsaturated Uronic Acid Residues of Glycosamtnoglycan Disaccharides

Molecular mechanics calculations (using the REFINE package) have been performed on a series of disaccharides obtained by cleavage of glycosaminoglycans with lyases, in order to examine the effect of chemical environment on the conformation of the 4,5-unsaturated uronic acid residue. The disaccharides were derived from heparin and heparan sulfate (1–5), hyaluronic acid (6), chondroitin (7), chondroitin-4-sulfate (8), and chondroitin-6-sulfate (9). The 1H NMR spectra were analysed for the above compounds and for the unsaturated uronic acid residues of a low-molecular weight E. Coli K5 polysaccharide (10), as well as for the alditol derivative (11) of compound 8; the wide variation of the interproton vicinal coupling constants as a function of configuration and position of the glycosidic linkages and of the sulfation pattern is unequivocally interpreted in terms of equilibrium between two distinct ring forms, namely 2H1 and 1H2. The equilibrium is semi-quantitatively explained by the results of the present energy calculations.