Structural heterogeneity of dermatan sulfate chains: correlation with heparin cofactor II activating properties.

To obtain dermatan sulfate (DS) with different structural characteristics and biological properties we isolated three groups of chains from a bovine mucosal DS preparation, differently iduronated and sulfated. The selected DS chains were characterized by their total charge values, electrophoretic mobility, susceptibility to Chondroitinase AC II treatment and disaccharide composition of Chondroitinase ABC digests. Besides the major IdoUA---> GalNac-4-SO4 sequences, two DS fractions (s-DS 1.75 M and f-DS 1.75 M) contained more than 10% disulfated disaccharides sequences and the third DS fraction (s-DS 1.5 M) contained only 4% disulfated disaccharides. Chondroitinase AC II treatment indicated that both the electrophoretically retarded forms (s-DS) are iduronic acid rich, as they were only minimally degraded to disaccharides/oligosaccharides. The ability of DS crude preparation to activate the heparin cofactor II (HCII) mediated inhibition of thrombin depends on the relative amount of highly active DS chains; this activity is related to the overall charge of DS chains and particularly with the content of IdoUA-2-SO4--->GalNAc-4-SO4 and UA--->GalNAc-4,6-di-SO4 disaccharides.