Unveiling the Disaccharide-Branched Glycosaminoglycan and Anticoagulant Potential of Its Derivatives

doi:10.1021/acs.biomac.0c01739

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	Unveiling the Disaccharide-Branched Glycosaminoglycan and Anticoagulant Potential of Its Derivatives
	Yin,Ronghua ; Zhou,Lutan ; Gao,Na ; Lin,Lisha ; Sun,Huifang ; Chen,Dingyuan; Cai,Ying ; Zuo,Zhili; Hu,Kaifeng; Huang,Shengxiong; Liu,Jikai ; Zhao,Jinhua
	2021
Source Publication	BIOMACROMOLECULES
ISSN	1525-7797
Volume	22 Issue:3 Pages:1244-1255
Abstract	Glycosaminoglycans (GAGs) are conserved polysaccharides composed of linear repeating disaccharides and play crucial roles in multiple biological processes in animal kingdom. However, saccharide-branched GAGs are rarely found, except the fucose-branched one from sea cucumbers. There was conjecture about the presence of disaccharide-branched GAG since 30 years ago, though not yet confirmed. Here, we report a GAG containing galactose-fucose branches from Thelenota ananas. This unique branch was confirmed as D-Gal(4)S(6S)-alpha 1,2-L-Fuc(3S) by structural elucidation of oligosaccharides prepared from T. ananas GAG. Bioassays indicated that oligomers with a larger degree of polymerization exhibited a potent anticoagulation by targeting the intrinsic tenase. Heptasaccharide was proven as the minimum fragment retaining the anticoagulant potential and showed 92.6% inhibition of venous thrombosis in vivo at sc. of 8 mg/kg with no obvious bleeding risks. These results not only solve a long-standing question about the presence of disaccharide-branched GAG in Holothuroidea, but open up new opportunities to develop safer anticoagulants.
Keyword	FUCOSYLATED CHONDROITIN SULFATE DEPOLYMERIZED HOLOTHURIAN GLYCOSAMINOGLYCAN INTRINSIC TENASE COMPLEX SEA-CUCUMBER FUCOSE BRANCHES BODY-WALL INDEPENDENT INHIBITION POLYSACCHARIDE ACCOUNT FACTOR XASE HEPARIN
DOI	10.1021/acs.biomac.0c01739
WOS ID	WOS:000627592800019
Citation statistics	Cited Times:11[WOS] [WOS Record] [Related Records in WOS]
Document Type	期刊论文
Identifier	http://ir.kib.ac.cn/handle/151853/73466
Collection	中国科学院昆明植物研究所
Affiliation	1.South Cent Univ Nationalities, Sch Pharmaceut Sci, Wuhan 430074, Peoples R China 2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
Recommended Citation GB/T 7714	Yin,Ronghua,Zhou,Lutan,Gao,Na,et al. Unveiling the Disaccharide-Branched Glycosaminoglycan and Anticoagulant Potential of Its Derivatives[J]. BIOMACROMOLECULES,2021,22(3):1244-1255.
APA	Yin,Ronghua.,Zhou,Lutan.,Gao,Na.,Lin,Lisha.,Sun,Huifang.,...&Zhao,Jinhua.(2021).Unveiling the Disaccharide-Branched Glycosaminoglycan and Anticoagulant Potential of Its Derivatives.BIOMACROMOLECULES,22(3),1244-1255.
MLA	Yin,Ronghua,et al."Unveiling the Disaccharide-Branched Glycosaminoglycan and Anticoagulant Potential of Its Derivatives".BIOMACROMOLECULES 22.3(2021):1244-1255.

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