Interactions between depolymerized fucosylated glycosaminoglycan and coagulation proteases or inhibitors
文献类型:期刊论文
作者 | Xiao, Chuang1,2![]() ![]() |
刊名 | THROMBOSIS RESEARCH
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出版日期 | 2016-10-01 |
卷号 | 146页码:59-68 |
关键词 | Fucosylated glycosaminoglycan coagulation proteases biolayer interferometry binding kinetics structure-activity relationship |
英文摘要 | Fucosylated glycosaminoglycan (FG) is a structurally novel glycosaminoglycan derivative, and if has potent. anticoagulant. activity. Depolymerized FG (dFG) is a selective factor Xase (FXase, FIXa-FVIIIa complex) inhibitor and iL has anfilhromboLic action without major bleeding risks. In this study, we report the effects of LIFG-3 (Mw similar to 14 kDa) on the catalysis rates of factor lb (lla), factor Xa (FXa) and labor IXa (FIXa) inhibition by anti thrombin (AT), and Lhe kinetic of the interactions between coagulation proteases or inhibitors and dFG-3 were also studied using biolayer interferometry (BLI) technology. We found that dFG-3 had much weaker catalysis activity of coagulation proteases inhibition by AT compared with heparin (UFH).The binding affinity of AT bound to dFG-3 was lower than UFH, and the UFH-AT interaction fitted well with biphasic-binding model while dFG-3-AT interaction was monophasic-binding, suggesting dFG-3 might not have allosteric activation effect on AT. The results are consistent with AT-independent inhibitory activities of dFG-3. dFG-3 could strongly bind to FIXa with much higher affinity than UFH, further explained the reason for its potent FXase inhibitory activity. Additionally, the binding ability of dFG-3 and FIXa decreased with decreasing molecular, and the fucose side chains and carboxyl groups of dFG-3 might be required for its high affinity binding with FIXa. Our data supports further the investigation of dFG-3 as a promising anticoagulant drug inhibiting the intrinsic FXase by binding W FIXa. (C) 2016 Elsevier Ltd. All rights reserved. |
类目[WOS] | Hematology ; Peripheral Vascular Disease |
研究领域[WOS] | Hematology ; Cardiovascular System & Cardiology |
关键词[WOS] | FREE-RADICAL DEPOLYMERIZATION ; MOLECULAR-WEIGHT FRACTIONS ; CUCUMBER THELENATA-ANANAS ; INTRINSIC TENASE COMPLEX ; HOLOTHURIAN GLYCOSAMINOGLYCAN ; CHONDROITIN SULFATE ; FACTOR-IXA ; ANTICOAGULANT ACTIVITIES ; ANTITHROMBIN-III ; TERNARY COMPLEX |
收录类别 | SCI |
语种 | 英语 |
WOS记录号 | WOS:000386232100011 |
源URL | [http://ir.kib.ac.cn/handle/151853/33649] ![]() |
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, Yunnan Key Lab Nat Med Chem, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Sun Yat Sen Univ, Coll Life Sci, Guangzhou 510275, Guangdong, Peoples R China |
推荐引用方式 GB/T 7714 | Xiao, Chuang,Lian, Wu,Zhou, Lutan,et al. Interactions between depolymerized fucosylated glycosaminoglycan and coagulation proteases or inhibitors[J]. THROMBOSIS RESEARCH,2016,146:59-68. |
APA | Xiao, Chuang.,Lian, Wu.,Zhou, Lutan.,Gao, Na.,Xua, Li.,...&Zhao, Jinhua.(2016).Interactions between depolymerized fucosylated glycosaminoglycan and coagulation proteases or inhibitors.THROMBOSIS RESEARCH,146,59-68. |
MLA | Xiao, Chuang,et al."Interactions between depolymerized fucosylated glycosaminoglycan and coagulation proteases or inhibitors".THROMBOSIS RESEARCH 146(2016):59-68. |
入库方式: OAI收割
来源:昆明植物研究所
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