Conformation of the Unsaturated Uronic Acid Residues of Glycosamtnoglycan Disaccharides

Abstract

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.