硫酸酯基的位置与纤维素硫酸酯抗凝血活性关系

采用直接硫酸酯化法和定向硫酸酯化法制备硫酸酯基分别在C-6、C-2和C-6,2的3种纤维素硫酸酯CSC6、CSC2和CSC6,2，并分别通过凝血时间和凝血因子活性分析研究其抗凝血活性，以揭示硫酸酯基的位置与纤维素硫酸酯抗凝血活性之间的构效关系.结果表明，CSC6,2延长凝血酶时间（tTT）和抑制凝血因子Ⅱa的活性突出，CSC2具有较强延长部分凝血活酶时间（tAPTT）和抑制凝血因子Ⅹa的活性，CSC6的抗凝血效果和对凝血因子的抑制作用均不如前二者.硫酸酯基的位置影响纤维素硫酸酯糖链的伸展程度和空间构象，导致其与抗凝血酶ATⅢ的结合程度不同，从而产生不同的抑制Ⅱa、Ⅹa和延长tAPTT、tTT的效果.

Relationship between site of sulfate groups in cellulose sulfate and their anticoagulation activity

Three cellulose sulfates (CS) with their sulfate groups only at C-6 position (CSC6), only at C-2position (CSC2), and at some C-6 &; C-2 positions (CSC6,2) were prepared respectively by the direct sulfation method and the regioselective sulfation method. To reveal the structure-activity relationship between sulfate groups and anticoagulation activities of CS, their anticoagulation activities were investigated by measurement of coagulation time and coagulation factor activity assays. It was indicated that CSC6,2 could significantly prolong thrombin time (tTT) and inhibit the activity of coagulation factor Ⅱa, also CSC2 had a pronounced activity of prolongation of activated partial thromboplastin time (tAPTT) and inhibition of the coagulation factorⅩa. Comparatively the anticoagulation activity and the inhibition of the coagulation factors of CSC6 were weaker than those of CSC6,2 or CSC2. The site of the sulfate groups in CS influnced the flexibility and conformation of the glycan chains, resulting in the different affinity of CS and antithrombin Ⅲ (AT Ⅲ).Thus, the prolongation of tAPTT&; tTT and the inhibition of Ⅱa &; Ⅹa of CS was associated with the site of the sulfate groups in CS.