Discovery of an intrinsic tenase complex inhibitor: Pure nonasaccharide from fucosylated glycosaminoglycan

doi:10.1073/pnas.1504229112

	Discovery of an intrinsic tenase complex inhibitor: Pure nonasaccharide from fucosylated glycosaminoglycan
	Zhao, Longyan; Wu, Mingyi; Xiao, Chuang; Yang, Lian; Zhou, Lutan; Gao, Na; Li, Zi; Chen, Jun; Chen, Jianchao; Liu, Jikai; Qin, Hongbo; Zhao, Jinhua
	2015-07-07
发表期刊	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷号	112 期号:27 页码:8284-8289
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.
关键词	Anticoagulant Inhibitors Oligosaccharides Carbohydrates Drug Discovery
DOI	10.1073/pnas.1504229112
收录类别	SCI
语种	英语
WOS记录号	WOS:000357527600052
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/24978
专题	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.

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