不同硫酸双糖簇对不同来源硫酸皮肤素通过HCII介导的凝血酶抑制作用的相对影响。
Relative influence of different disulphate disaccharide clusters on the HCII-mediated inhibition of thrombin by dermatan sulphates of different origins.
作者信息
Mascellani G, Liverani L, Prete A, Guppola P A, Bergonzini G, Bianchini P
机构信息
Opocrin S.p.A. Research and Development Laboratories, Corlo, Italy.
出版信息
Thromb Res. 1994 Jun 15;74(6):605-15. doi: 10.1016/0049-3848(94)90217-8.
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.
除了主要的单硫酸化二糖序列（艾杜糖醛酸-4-O-硫酸乙酰半乳糖胺）外，硫酸皮肤素（DS）还含有过度硫酸化序列（2-O-硫酸艾杜糖醛酸-4-O-硫酸乙酰半乳糖胺）和（艾杜糖醛酸-4,6-O-二硫酸乙酰半乳糖胺），其浓度与DS介导的HCII对凝血酶的抑制作用相关。研究了化学去除硫酸基团对HCII介导活性的影响。碱催化从2-O-硫酸艾杜糖醛酸残基上取代硫酸基团，导致环氧-α-古洛糖醛酸的形成，这是一级反应。当（艾杜糖醛酸-4,6-O-二硫酸乙酰半乳糖胺）序列的含量高于（2-O-硫酸艾杜糖醛酸-4-O-硫酸乙酰半乳糖胺）序列时，从2-O-硫酸艾杜糖醛酸上去除硫酸基团对HCII活性的降低作用小于后一种序列占主导时。（艾杜糖醛酸-4,6-O-二硫酸乙酰半乳糖胺）与（2-O-硫酸艾杜糖醛酸-4-O-硫酸乙酰半乳糖胺）协同激活HCII。此外，在不存在2-O-硫酸艾杜糖醛酸-4-O-硫酸乙酰半乳糖胺的情况下，从4,6-O-二硫酸乙酰半乳糖胺上去除6-O-硫酸基团也会显著降低活性。一种富含2-O-硫酸艾杜糖醛酸以及葡萄糖醛酸的低分子量天然组分，其电泳迁移率高于含有较少葡萄糖醛酸的高分子量DS，具有显著的活性。
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