RELATIVE INFLUENCE OF DIFFERENT DISULFATE DISACCHARIDE CLUSTERS ON THE HCII-MEDIATED INHIBITION OF THROMBIN BY DERMATAN SULFATES OF DIFFERENT ORIGINS

Besides the major monosulphated disaccharide sequences (IdoA-GalNAc4SO(3)), dermatan sulphates (DS) contain the oversulphated sequences (IdoA2SO(3)-GalNAc4SO(3)) and (IdoA-GalNAc4,6SO(3)), the concentration of which is correlated with the HCII-mediated inhibition of thrombin by DS. The effect of the chemical removal of the sulphate groups on the HCII-mediated activity was studied. The base-catalyzed sulphate group displacement from IdoA2SO(3) residues, leading to formation of the epoxyde aGulA, is a 1st order reaction. When the content of sequences (IdoA-GalNAc4, 6SO(3)) is higher than that of sequences (IdoA2SO(3)-GalNAc4SO(3)), removal of the sulphate groups from Ido2SO(3) reduces the HCII activity less than when the latter sequences prevail. (IdoA-GalNAc4, 6SO(3)) cooperates with (IdoA2SO(3)-GalNAc4SO(3)) in the activation of the HCII. Also the removal of 6-SO3- groups from GalNAc4, 6SO(3), in absence of IdoA2SO(3)-GalNAc4SO(3), considerably reduces the activity. A low molecular mass natural fraction rich in IdoA2SO(3) as well as glucuronic acid, having higher electrophoretic mobility than the higher molecular mass DS which contains less glucuronic acid, is remarkably active.