A new fucosylated glycosaminoglycan containing disaccharide branches from Acaudina molpadioides: Unusual structure and anti-intrinsic tenase activity. (1st October 2020)

• Record Type: Journal Article
• Authors: Mao, Hui; Cai, Ying; Li, Shanni; Sun, Huifang; Lin, Lisha; Pan, Ying; Yang, Wenjiao; He, Zhicheng; Chen, Ru; Zhou, Lutan; Wang, Weili; Yin, Ronghua; Zhao, Jinhua
• Is Part Of: Carbohydrate polymers. Volume 245(2020)
• Publication Date: 2020-10-01
• Subjects: FG fucosylated glycosaminoglycan -- iXase intrinsic factor tenase complex -- FS fucan sulfate -- CS chondroitin sulfate -- GlcUA β-D-glucuronic acid -- GalNAc N-acetyl-β-D-galactosamine -- Fuc α-L-fucose -- Fuc2S4S 2, 4-di-O-sulfated fucose -- Fuc3S4S 3, 4-di-O-sulfated fucose -- Fuc4S 4-mono-O-sulfated fucose -- AmFG FG from Acaudina molpadioides -- HaFG FG from Holothuria albiventer -- dAmFG β-eliminative depolymerized product of AmFG -- dAmFG' free-radical depolymerized product of AmFG -- dp degree of polymerization -- IEC ion-exchange chromatography -- GPC gel permeation chromatography -- HPGPC high-performance gel permeation chromatography -- APTT activated partial thromboplastin time -- PT prothrombin time -- TT thrombin time -- AT antithrombin -- FIIa coagulant factor IIa -- FXa coagulant factor Xa -- RID differential refractive index detector -- DAD diode array detector -- Mw weight-average molecular weight -- LMWH low molecular weight heparin -- TSP trimethylsilyl-propionic acid; Disaccharide branch -- Fucosylated glycosaminoglycan -- Oligosaccharide -- Anticoagulant -- Intrinsic tenase; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2020.116503
• Languages: English
• ISSNs: 0144-8617

Abstract

Highlights: A novel FG (AmFG) were extracted from sea cucumber Acaudina molpadioides . The structures of eight oligosaccharides from depolymerized AmFG were determined. AmFG branched with unusual disaccharide GalNAc-α1, 2-Fuc, besides monosaccharides. The anticoagulant and anti-iXase activities of AmFG and oligomers were discussed. Abstract: A fucosylated glycosaminoglycan (AmFG) was extracted from the sea cucumber Acaudina molpadioides . And a series of oligosaccharides were purified from the size-homogeneous fractions, which were prepared from the β-eliminative depolymerized AmFG. According to "bottom-up" strategy, the precise structure of AmFG was elucidated by analyzing the structures of these purified oligosaccharides, combining with NMR analysis of its free-radical depolymerized product. It contained a CS-E-like backbone, and each GlcUA was branched with a mono- or di-sulfated fucose (Fuc) at O -3. Intriguingly, besides two types of monosaccharide branches, Fuc2S4S (60 %) and Fuc4S (25 %), that were common in FG, AmFG also contained an unusual disaccharide branch GalNAc-α1, 2-Fuc3S4S (15 %); this is the first report of such a structure in a glycosaminoglycan. Biological assays indicated that native AmFG and its oligosaccharides had potent anticoagulant and intrinsic tenase (iXase) inhibitory activities in a chain length-dependent manner. For these oligosaccharides, octasaccharide was the minimum structural fragment for potent anti-iXase activity, and the disaccharide branch might enhance this activity.