Relative influence of different disulphate disaccharide clusters on the HCII-mediated inhibition of thrombin by dermatan sulphates of different origins

Besides the major monosulphated disaccharide sequences (IdoA-GalNAc4SO₃), dermatan sulphates (DS) contain the oversulphated sequences (IdoA2SO₃-GalNAc4SO₃) and (IdoA-GalNAc4,6SO₃), 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 IdoA2SO₃ residues, leading to formation of the epoxyde aGulA, is a 1st order reaction. When the content of sequences (IdoA-GalNAc4,6SO₃) is higher than that of sequences (IdoA2SO₃-GalNAc4SO₃), removal of the sulphate groups from Ido2SO₃ reduces the HCII activity less than when the latter sequences prevail. (IdoA-GalNAc4,6SO₃) cooperates with (IdoA2SO₃-GalNAc4SO₃) in the activation of the HCII. Also the removal of 6-SO₃ groups from GalNAc4,6SO₃, in absence of IdoA2SO₃-GalNAc4SO₃, considerably reduces the activity. A low molecular mass natural fraction rich in IdoA2SO₃ as well as glucuronic acid, having higher electrophoretic mobility than the higher molecular mass DS which contains less glucuronic acid, is remarkably active.