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Biomacromolecules 2021 Mar 08;223:1244-1255. doi: 10.1021/acs.biomac.0c01739.
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Unveiling the Disaccharide-Branched Glycosaminoglycan and Anticoagulant Potential of Its Derivatives.

Yin R , Zhou L , Gao N , Lin L , Sun H , Chen D , Cai Y , Zuo Z , Hu K , Huang S , Liu J , Zhao J .

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-Gal4S(6S)-α1,2-l-Fuc3S 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.

PubMed ID: 33616386
Article link: Biomacromolecules