分子模拟应用于岩藻糖化糖胺聚糖 3D 结构确定及其与内源 性因子 X 酶的相互作用模式考察

	分子模拟应用于岩藻糖化糖胺聚糖 3D 结构确定及其与内源性因子 X 酶的相互作用模式考察; Application of molecular simulation in the determination of the 3D structure of fucosylated glycosaminoglycan and its interaction with iXase
	陈鼎元
导师	左之利
摘要	Thrombosis is a potentially serious, often a fatal health disease and that is mainly caused by the formation of microscopic blood clots in arteries and capillaries of the human body. It is quite common in most developed countries in the world. Nowadays, most of the clinically approved anticoagulants tend various side effects such as severe bleeding, abdominal pain, flatulence, headache, lethargy, dizziness, nausea. anemia,etc. Besides, recent studies also revealed that an intrinsic anticoagulant pathway is not also played a crucial role in the formation of thrombosis. Therefore, there is an urgent need to develop a selectively inhibit intrinsic coagulation factors, which become a new trend in the discovery of new and novel anticoagulants with the low risk of side effects. Fucosylated glycosaminoglycan (FG) is a kind of novel and structurally complex acidic polysaccharide with a wide range of pharmacological activities such as antitumor, anti-hyperlipidemia, anti-hyperglycemia, anti-inflammatory, antiviral properties. Moreover, the structure-activity relationship (SAR) studies of FG and its depolymerized products with various molecular weights reveal that FG has a potent and selective inhibition of intrinsic Xase (iXase) activity and anticoagulant properties. The intrinsic Xase complex (iXase) is an important key speed limiting step in the last active site of the endogenous coagulation pathway. Due to the limitations of techniques, the crystal structure of iXase and their interaction with FG has not been clearly described, so far. In this research the computer-aided drug design was used to explore the active spatial conformational structures of FG and the characteristic chemical reaction of various structural features and, the spatial structure of iXase was constructed to further explore the binding sites and structure-activity relationships of FG and iXase interactions. 1. Determination of 3D-spatial conformation of FG oligosaccharides. To explore the interaction mechanism between FGs oligosaccharides and iXase and to explain the various characteristics chemical structure of FGs oligosaccharides and various sulfation position of the fucose lead to different sensitivity to elimination depolymerization. Based on the previous studies, the active spatial conformation of FGs oligosaccharides and their derivatives was determined to employ quantitative calculation and computer-aided drug design. 1). The active spatial conformation of 14 depolymerized FG products with known iXase inhibitory activity, two-dimensional structure and, the spatial conformation of repeated structural units of FG were determined. Besides the active oligosaccharide database was also constructed for the following study of the interaction between FGs and iXase. 2).Determination of containing Fucose（Fuc）at different positions of sulfating branched-chain quaternary ammonium salt of FG activity space conformation, found with Fuc2S4S and Fuc3S4S quaternary ammonium salt have obvious d
	2021-05
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74108
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	陈鼎元. 分子模拟应用于岩藻糖化糖胺聚糖 3D 结构确定及其与内源性因子 X 酶的相互作用模式考察, Application of molecular simulation in the determination of the 3D structure of fucosylated glycosaminoglycan and its interaction with iXase[D],2021.

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