Structural Characterization and Anticoagulant Potential of Fucosylated Glycosaminoglycan 5-12 Oligomers with Unusual Branches.

The depolymerized products and oligosaccharide fractions from sea cucumber fucosylated glycosaminoglycans (FGs) are promising anticoagulant candidates, and more novel FG-derived oligosaccharides from low-priced sea cucumbers are expected to be obtained. This study isolated 5-12 oligomers (OF1-OF3) with unusual branches from β-eliminative depolymerized products of FG (CqFG). Detailed NMR analyses showed that OF1-OF3 consisted of a chondroitin 4,6-sulfates backbone and some sulfated fucosyl branches (FucS), including monosaccharides (α-l-Fuc, α-l-Fuc, α-l-Fuc, α-l-Fuc, and α-l-Fuc) and a disaccharide D-Gal-α1,3-l-Fuc with the ratio of ~36:35:10:7:3:9, attached to the C-3 position of β-d-GlcA or its derivatives, such as α-l-Δ4,5GlcA and β-d-GlcA-ol. Unusually, α-l-Fuc was the main FucS branch; no α-l-Fuc branch was found, and α-l-Fuc and α-l-Fuc branches were also found in OF1-OF3. The OF2 and OF3 could strongly inhibit the intrinsic and common coagulation pathways. Intrinsic FXase is a target of OF2 and OF3 inhibiting the intrinsic coagulation pathways, and the unusual side chains may increase the intrinsic FXase inhibitory activity. OF2 and OF3 showed negligible bleeding risk, and less bleeding than heparin (HP), low-molecular-weight heparins (LMWHs), and CqFG. These findings support novel FG oligosaccharides with some unusual branches from low-priced sea cucumbers to be prepared as safer anticoagulants.