Conformational studies of proteoglycans: theoretical studies on the conformation of heparin

Abstract

Various models proposed for heparin have been examined by a stereochemical approach involving contact distance criteria and potential energy calculations. The present study suggests that the model favored by Atkins and coworkers [Biochem. J. (1973) 135, 729-733 and (1974) 143, 251-252] is not stereochemically satisfactory. An alternative model has been proposed with N-acetyl-D-glucosamine and one of the uronides in the ⁴C₁ conformation and the other uronide (probably sulfated) in the ¹C₄ conformation. The observed variations in the tetrasaccharide periodicities (16.5-17.3 Å) in different crystalline modifications of heparin have been attributed to possible changes in the rotational angles about the interunit glycosidic bonds rather than a change in the pyranose ring conformation. The proposed model is also independent of the observed variation in the relative composition of uronic acid residues in heparin. These conclusions are in disagreement with those of earlier workers.