Precise structures of fucosylated glycosaminoglycan and its oligosaccharides as novel intrinsic factor Xase inhibitors
Shang, Feineng1,2; Gao, Na1,3; Yin, Ronghua1; Lin, Lisha1; Xiao, Chuang1; Zhou, Lutan1; Li, Zi1; Purcell, Steven W.4; Wu, Mingyi1; Zhao, Jinhua1
2018-03-25
发表期刊EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN0223-5234
卷号148页码:423-435
摘要Selective inhibition of the endogenous coagulation pathway is a promising strategy for developing new anticoagulants. Fucosylated glycosaminoglycan (FG), a structurally complex glycosaminoglycan, has distinct anticoagulant properties, especially the strong intrinsic factor Xase inhibitory activity that is recognized as a new target with potential physiological and therapeutic applications. Detailed knowledge of FG structures is necessary for developing a clinically effective intrinsic FXase inhibitor. However, challenges remain to elucidate FG structures as a basis for pharmaceutical development. Herein, using the highly selective beta-elimination method, oligosaccharides with regular structures were prepared from the depolymerization products. Analysis of oligosaccharides further confirmed the precise structural sequence of the FG. Furthermore, biological activity assay suggested that these pure homogeneous oligosaccharides, particularly an octasaccharide, exhibit strong inhibition of the intrinsic coagulation pathway by inhibiting human intrinsic factor Xase. Our finding is significant for discovery of a new class of anticoagulant agents as intrinsic factor Xase inhibitors. (C) 2018 Elsevier Masson SAS. All rights reserved.
关键词Glycosaminoglycan Oligosaccharide Anticoagulant Intrinsic Factor Xase
语种英语
引用统计
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/60504
专题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, Yunnan, Peoples R China
2.Dali Univ, Sch Chem & Pharm, Dali 671003, Peoples R China
3.South Cent Univ Nationalities, Sch Pharmaceut Sci, Wuhan 430074, Hubei, Peoples R China
4.Southern Cross Univ, Natl Marine Sci Ctr, Coffs Harbour, NSW 2480, Australia
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Shang, Feineng,Gao, Na,Yin, Ronghua,et al. Precise structures of fucosylated glycosaminoglycan and its oligosaccharides as novel intrinsic factor Xase inhibitors[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2018,148:423-435.
APA Shang, Feineng.,Gao, Na.,Yin, Ronghua.,Lin, Lisha.,Xiao, Chuang.,...&Zhao, Jinhua.(2018).Precise structures of fucosylated glycosaminoglycan and its oligosaccharides as novel intrinsic factor Xase inhibitors.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,148,423-435.
MLA Shang, Feineng,et al."Precise structures of fucosylated glycosaminoglycan and its oligosaccharides as novel intrinsic factor Xase inhibitors".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 148(2018):423-435.
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