Anticoagulant and antithrombotic evaluation of native fucosylated chondroitin sulfates and their derivatives as selective inhibitors of intrinsic factor Xase

CORC > 昆明植物研究所 > 中国科学院昆明植物研究所 > 植物化学与西部植物资源持续利用国家重点实验室

	Anticoagulant and antithrombotic evaluation of native fucosylated chondroitin sulfates and their derivatives as selective inhibitors of intrinsic factor Xase
	Wu, Mingyi 1; Wen, Dandan 1,2; Gao, Na 1; Xiao, Chuang1,3 ; Yang, Lian 1; Xu, Li 1; Lian, Wu 1,3; Peng, Wenlie 3; Jiang, Jianmin 2; Zhao, Jinhua1
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2015-03-06
卷号	92 页码:257-269
关键词	Fucosylated chondroitin sulfate Factor Xase inhibitor Anticoagulant Antithrombotic Structure-activity relationship
通讯作者	Jiang,JM (reprint author),Sun Yat Sen Univ,Sch Pharmaceut Sci,Guangzhou 510006,Guangdong,Peoples R China. ; lssjjm@mail.sysu.edu.cn ; zhao.jinhua@yahoo.com
英文摘要	Fucosylated chondroitin sulfate (FCS), a structurally unusual glycosaminoglycan, has distinct anticoagulant properties, and is an especially strong inhibitor of the intrinsic factor Xase (anti-Xase). To obtain a highly selective inhibitor of human Xase, we purified six native FCSs with various sulfation patterns, prepared a series of FCS derivatives, and then elucidated the relationship between the structures and the anticoagulant activities of FCSs. FCSs 1-3 containing higher Fuc2S4S exhibit stronger AT-dependent anti-IIa activities, whereas 4-6 containing more Fuc3S4S produce potent HCII-dependent anti-IIa activities. Saccharides containing a minimum of 6-8 trisaccharide units, free carboxyl groups, and full fucosylation of GlcA may be required for potent anti-Xase activity, and approximately six trisaccharide units and partial fucosylation of GlcA may contribute to potent HCII-dependent activity. Decreasing of the molecular weights markedly reduces their AT-dependent anti-IIa activities, and even eliminates human platelet and factor XII activation. Furthermore, in vitro and in vivo studies suggested that fractions of 6-12 kDa may be very promising compounds as putative selective intrinsic Xase inhibitors with antithrombotic action, but without the consequences of major bleeding and factor XII activation. (C) 2014 Elsevier Masson SAS. All rights reserved.
学科主题	Chemistry, Medicinal
类目[WOS]	Chemistry, Medicinal
研究领域[WOS]	Pharmacology & Pharmacy
关键词[WOS]	DEPOLYMERIZED HOLOTHURIAN GLYCOSAMINOGLYCAN ; STICHOPUS-JAPONICUS SELENKA ; MOLECULAR-WEIGHT HEPARINS ; SEA-CUCUMBER ; FACTOR-IXA ; PHYSICOCHEMICAL CHARACTERISTICS ; POLYSACCHARIDE ACCOUNT ; BLOOD PLATELETS ; FUCOSE BRANCHES ; THROMBIN
收录类别	SCI
语种	英语
WOS记录号	WOS:000350919100020
内容类型	期刊论文
源URL	[http://ir.kib.ac.cn/handle/151853/20615]
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
作者单位	1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Peoples R China 2.Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China 3.Sun Yat Sen Univ, Coll Life Sci, Guangzhou 510006, Guangdong, Peoples R China
推荐引用方式 GB/T 7714	Wu, Mingyi,Wen, Dandan,Gao, Na,et al. Anticoagulant and antithrombotic evaluation of native fucosylated chondroitin sulfates and their derivatives as selective inhibitors of intrinsic factor Xase[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2015,92:257-269.
APA	Wu, Mingyi.,Wen, Dandan.,Gao, Na.,Xiao, Chuang.,Yang, Lian.,...&Zhao, Jinhua.(2015).Anticoagulant and antithrombotic evaluation of native fucosylated chondroitin sulfates and their derivatives as selective inhibitors of intrinsic factor Xase.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,92,257-269.
MLA	Wu, Mingyi,et al."Anticoagulant and antithrombotic evaluation of native fucosylated chondroitin sulfates and their derivatives as selective inhibitors of intrinsic factor Xase".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 92(2015):257-269.