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复杂FG的确切结构及其取代基对Xase抑制活性的影响

复杂FG的确切结构及其取代基对Xase抑制活性的影响
  • 导航:首页 > 科学基金
  • 批准号:81673330
  • 批准年度: 2016年
  • 学科分类:天然药物化学(H3002) |
  • 项目负责人:吴明一
  • 负责人职称:副研究员
  • 依托单位:中国科学院昆明植物研究所
  • 资助金额:52万元
  • 项目类别:面上项目
  • 研究期限:2017年01月01日 至 2020年12月31日
  • 中文关键词: 确切;取代基;Xase;活性
  • 英文关键词:Fucosylated glycominoglycan;Purified oligosaccharide;Precise chemical structure;Xase;Structure-activ

项目摘要

中文摘要

岩藻糖化糖胺聚糖(FG)是海洋棘皮动物来源的化学结构特殊的强效内源性因子X酶(Xase)抑制剂。选择性Xase抑制剂可能具有低出血倾向的强效抗血栓活性特点,深入的FG化学及药理学研究具有重要的学术及潜在应用价值。30多年来,天然FG因其结构复杂且为多糖混合物,其确切结构(如取代基确切结构类型及连接位置)尚存疑问,构效关系研究严重受限。本课题前期在规则结构FG的纯化寡糖结构片段研究中已取得积极进展,并在复杂FG的探索研究中发现其中可能存在二糖侧链、GlcUA硫酸酯基取代等特殊的结构类型。在此基础上,本课题拟采用糖苷键选择性解聚以及寡糖纯化技术制备获得多种类型的FG的纯化寡糖片段,通过寡糖结构解析阐明天然FG的确切结构特征与类型;通过纯化寡糖构效关系研究阐明不同取代基对其Xase抑制活性的影响,以期发现结构简单的强效选择性Xase抑制剂,为低出血倾向的抗血栓药物研发及其药理研究提供科学依据。

英文摘要

Fucosylated glycosaminoglycan (FG) is a potent intrinsic Xase inhibitor with unusual structure from sea echinoderm. Since selective Xase inhibitor may be a potential type of anticoagulant with low hemorrhage tendency, it is valuable to process further studies on chemistry and pharmacology of complex FGs. However, for 30 years, studies on elucidation of the precise structure of FG and its structure-activity relationship were severely limited for the mixture property of FG, for example sulfation patterns and glycosidic linkage types of side-chain substituents are still unclear. In our earlier researches, we found that FG might have some special structural types, such as disaccharide in its side chain and sulfation of GlcUA. And we also made significant advances on selective depolymerization of glucosidic bond in FG and purification of oligosaccharides with regular well-fined structure. Based on these, we will prepare pure oligosaccharides with different structures from native FG with representative structure types and explore the precise structures by structure analysis of purified oligosaccharides. Additionally, this project is further to study the structure–activity relationships of FGs to clarify the effect of different substitute groups on Xase inhibition activity. All of these aim to discover strong selective Xase inhibitor with simple chemical structure, and to further provide valuable information for new anticoagulant drugs with low hemorrhage tendency and their pharmacology studies.

评估说明

    国家自然科学基金项目“复杂FG的确切结构及其取代基对Xase抑制活性的影响”发布于爱科学iikx,并永久归类于相关科学基金导航中,仅供广大科研工作者查询、学习、选题参考。国科金是根据国家发展科学技术的方针、政策和规划,以及科学技术发展方向,面向全国资助基础研究和应用研究,发挥着促进我国基础研究源头创新的作用。国科金的真正价值在于它能否为科学进步和社会发展带来积极的影响。

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