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引用次数: 30
摘要
本文综述了肝素和硫酸肝素(HS)抗凝血作用的分子基础。一个高度特异的五糖序列,包含3- o -硫酸氨基葡萄糖,是这个作用的关键结构元素。综述了肝素和HS的生物合成。存在不同类型的HS蛋白多糖。对来自不同哺乳动物器官的HS制剂的分析表明,多糖的结构变异性是由于调控的聚合物修饰。除了抗凝血酶外,HS链在体内还能结合大量其他蛋白质。这种结合通常取决于不同单糖构建块的特定序列的存在,并且具有不同的含义。哺乳动物体内的许多生理和病理过程似乎都受到HS蛋白多糖的影响或调节。例如,HS链的正确组装被认为在正常胚胎和哺乳动物发育中起着重要作用。糖尿病、淀粉样变性和阿尔茨海默病等疾病可能与HS结构的变化有关。最后,讨论了基于HS化学的药物开发的可能性和策略。
This review article begins by discussing the molecular basis of the blood anticoagulant effect of heparin and some species of heparan sulphate (HS). A highly specific pentasaccharide sequence, containing a glucosamine 3-O-sulphate group, is a key structural element for this action. The biosynthesis of heparin and HS is outlined. Different types of HS proteoglycans exist. Analysis of HS preparations from different mammalian organs has indicated that the structural variability of the polysaccharide is due to regulated polymer modification. In addition to antithrombin, HS chains bind a very large number of other proteins in vivo. Such binding often appears to depend on the presence of specific sequences of different monosaccharide building-blocks and has diverse implications. Many physiological and pathological processes in the mammalian body appear to be influenced or regulated by HS proteoglycans. For example, the proper assembly of HS chains is believed to play an important role in normal embryonic and mammalian development. Diseases such as diabetes, amyloidosis and Alzheimer's may be associated with changes in HS structure. Finally, the possibilities and strategies for developing drugs based on HS chemistry are discussed.