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题名: Anticoagulant and antithrombotic evaluation of native fucosylated chondroitin sulfates and their derivatives as selective inhibitors of intrinsic factor Xase
作者: Wu, Mingyi1; Wen, Dandan1, 2; Gao, Na1; Xiao, Chuang1, 3; Yang, Lian1; Xu, Li1; Lian, Wu1, 3; Peng, Wenlie3; Jiang, Jianmin2; Zhao, Jinhua1
刊名: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
出版日期: 2015-03-06
卷号: 92, 页码:257-269
关键词: Fucosylated chondroitin sulfate ; Factor Xase inhibitor ; Anticoagulant ; Antithrombotic ; Structure-activity relationship
学科分类: Chemistry, Medicinal
DOI: 10.1016/j.ejmech.2014.12.054
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
文章类型: Article
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.
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
项目资助者: Yunnan Provincial Science and Technology Department in China [2010CI116, 2012FB177, 2013FA046] ; National Natural Science Foundation of China [81102372, 81373292] ; Outstanding Technical Talent Foundation of the Chinese Academy of Sciences ; West Light Foundation of the Chinese Academy of Sciences
语种: 英语
WOS记录号: WOS:000350919100020
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.kib.ac.cn/handle/151853/20615
Appears in Collections:植物化学与西部植物资源持续利用国家重点实验室_期刊论文

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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
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