中文摘要
天然来源的岩藻糖化糖胺聚糖(FG)是主链为硫酸软骨素 E (CS-E),而连有岩藻糖侧链的结构新颖的糖胺聚糖衍生物,具有显著依赖肝素辅因子II (HC-II) 的抗凝血酶活性,且强于选择性激活 HC-II 的抗凝药物硫酸皮肤素 (DS)。鉴于FG化学结构不同于DS,研究FG依赖 HC-II 抗凝血酶活性的药理作用机制及其构效关系具有重要的理论和应用价值。本项目通过纯化寡糖研究 FG寡糖链长及官能团对其依赖HC-II的抗凝血酶活性的药效强度、选择性及药物与靶点之间相互作用的动力学特征,阐明FG类化合物依赖HC-II的抗凝血酶的最短结构序列及其构效关系,并探讨 HC-II 的激活机制及其潜在应用价值。
英文摘要
Native fucosylated glycosaminoglycan (FG) is a mucopolysaccharide from sea cucumber composed of a chondroitin sufate E-like core with distinct sulfated fucose branches and it has potent anticoagulant activities. FG showed stronger effect on heparin cofactor II (HCII)-dependent inhibition of f.IIa activity than dermatan sulfate (DS), which is an anticoagulant drug with selective activation of HCII. The elucidation of SAR and mechanism of FG on HCII-dependent inhibition of f.IIa activity is of great value on theory and application in view of its different structure with DS. The effect of the degree of polymerization of FG derived oligosaccharides and their chemical groups on HCII-dependent inhibition of f.IIa activity were investigated in our research, as well as their interactions with target proteins.
