海地瓜（Acaudina molpadioides）酸性多糖 化学结构与抗凝活性研究

	海地瓜（Acaudina molpadioides）酸性多糖化学结构与抗凝活性研究; Chemical Structures and Anticoagulant Activities of Acidic Polysaccharides from Acaudina molpadioides
	毛慧
导师	赵金华
摘要	The acidic polysaccharides fucosylated glycosaminoglycan （FG） and fucan sulfate （FS） derived from marine echinoderms sea cucumbers have special chemical structures and extensive pharmacological activities. In particular, natural FG has strong anticoagulant activity, and its special pharmacological mechanism of inhibiting intrinsic tenase Xase makes it a leading compound for the study of new target anticoagulant and antithrombotic drugs. For nearly 40 years research, the basic structure of FG and its pharmacological mechanism for inhibiting iXase activity have gradually become clear. It is generally believed that FG has ammalianm Chondroitin Sulfate-like main chain alternately connected by D-β-GlcUAand D-β-GalNAc and a large number of sulfated substituted L-α-Fuc side chains. The inhibition of iXase activity by FG is related to its high affinity binding to IXa and affecting the formation of VIIIa-IXa complex, and the structure-activity relationship analysis shows that its activity intensity is related to the chain length. As seen so far, the FG octasaccharide sequence is the smallest structural fragment for strongly inhibits iXase. However, the structure of FGs from different species, are quite different. Therefore, the structural diversity of natural FG is worth further study and analysis. The precise structure of FGs, especially the side chain length and the substituted form of sulfate groups in some species, are still in doubt. The influence of the side chain with special chemical structures on their inhibition of iXase activity still needs further investigation. In order to further understand the structural diversity and pharmacological mechanism of sea cucumber acid polysaccharides, Polysaccharides from Acaudina molpadioides were systematically studied in the physicochemical properties, structural characteristics, anticoagulant activity, target mechanism of polysaccharides contained in the body wall and the structure-activity relationship of FG depolymerization products of different side chain types. For the FG（AmFG）derived from Acaudina molpadioides, the β-elimination depolymerization method with glycosidic bonds was used to obtain the FG depolymerization product, and the series of purified oligosaccharides containing different side chain substitution forms are isolated by GPC and SAX-HPLC preparation techniques. On this basis, the anticoagulant activity and target mechanism of acidic polysaccharides （FG and FS） derived from Acaudina molpadioides were systematically studied, Structure-activity relationship of FG structural fragments with different side chains was explored by iXase inhibitory activity of purified oligosaccharides which have different in side chain types. All of this provide valuable basic research data for the development of new target anticoagulant and antithrombotic drugs. In addition, the basic structural characteristics and anticoagulant activity of FS（AmFS）derived from Acaudina molpadioides were preliminarily discussed.
	2020-05
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74162
专题	昆明植物所硕博研究生毕业学位论文
推荐引用方式 GB/T 7714	毛慧. 海地瓜（Acaudina molpadioides）酸性多糖化学结构与抗凝活性研究, Chemical Structures and Anticoagulant Activities of Acidic Polysaccharides from Acaudina molpadioides[D],2020.

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