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

作者：Ronghua Yin, Lutan Zhou, Na Gao, Lisha Lin, Huifang Sun, Dingyuan Chen, Ying Cai, Zhili Zuo, Kaifeng Hu, Sheng‐Xiong Huang, Ji‐Kai Liu, Jinhua Zhao · 发表于：Biomacromolecules · 年份：2021 · DOI：10.1021/acs.biomac.0c01739 · 被引用次数：32 · 研究领域：Echinoderm biology and ecology、Seaweed-derived Bioactive Compounds、Marine Sponges and Natural Products

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 4S(6S) -α1,2- 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.