Discovery of an intrinsic tenase complex inhibitor: Pure nonasaccharide from fucosylated glycosaminoglycan
文献类型：期刊论文
| 作者 | Zhao, Longyan ; Wu, Mingyi; Xiao, Chuang; Yang, Lian; Zhou, Lutan; Gao, Na; Li, Zi; Chen, Jun; Chen, Jianchao; Liu, Jikai
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| 刊名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
 |
| 出版日期 | 2015-07-07 |
| 卷号 | 112期号:27页码:8284-8289 |
| 关键词 | anticoagulant inhibitors oligosaccharides carbohydrates drug discovery |
| 英文摘要 | Selective inhibition of the intrinsic coagulation pathway is a promising strategy for developing safer anticoagulants that do not cause serious bleeding. Intrinsic tenase, the final and rate-limiting enzyme complex in the intrinsic coagulation pathway, is an attractive but less explored target for anticoagulants due to the lack of a pure selective inhibitor. Fucosylated glycosaminoglycan (FG), which has a distinct but complicated and ill-defined structure, is a potent natural anticoagulant with nonselective and adverse activities. Herein we present a range of oligosaccharides prepared via the deacetylation-deaminative cleavage of FG. Analysis of these purified oligosaccharides reveals the precise structure of FG. Among these fragments, nonasaccharide is the minimum fragment that retains the potent selective inhibition of the intrinsic tenase while avoiding the adverse effects of native FG. In vivo, the nonasaccharide shows 97% inhibition of venous thrombus at a dose of 10 mg/kg in rats and has no obvious bleeding risk. This nonasaccharide may therefore serve as a novel promising anticoagulant. |
| 类目[WOS] | Multidisciplinary Sciences |
| 研究领域[WOS] | Science & Technology - Other Topics |
| 关键词[WOS] | DEPOLYMERIZED HOLOTHURIAN GLYCOSAMINOGLYCAN ; FREE-RADICAL DEPOLYMERIZATION ; CUCUMBER THELENATA-ANANAS ; MOLECULAR-WEIGHT HEPARIN ; CHONDROITIN SULFATE-E ; SEA-CUCUMBER ; VENOUS THROMBOEMBOLISM ; FACTOR-IXA ; BODY-WALL ; CHEMOENZYMATIC SYNTHESIS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000357527600052 |
| 源URL | [http://ir.kib.ac.cn/handle/151853/24978]  |
| 专题 | 昆明植物研究所_植物化学与西部植物资源持续利用国家重点实验室 |
| 推荐引用方式 GB/T 7714 | Zhao, Longyan,Wu, Mingyi,Xiao, Chuang,et al. Discovery of an intrinsic tenase complex inhibitor: Pure nonasaccharide from fucosylated glycosaminoglycan[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2015,112(27):8284-8289. |
| APA | Zhao, Longyan.,Wu, Mingyi.,Xiao, Chuang.,Yang, Lian.,Zhou, Lutan.,...&Zhao, Jinhua.(2015).Discovery of an intrinsic tenase complex inhibitor: Pure nonasaccharide from fucosylated glycosaminoglycan.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,112(27),8284-8289. |
| MLA | Zhao, Longyan,et al."Discovery of an intrinsic tenase complex inhibitor: Pure nonasaccharide from fucosylated glycosaminoglycan".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 112.27(2015):8284-8289. |
入库方式： OAI收割
来源：昆明植物研究所
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