Oligosaccharides from depolymerized fucosylated glycosaminoglycan: Structures and minimum size for intrinsic factor Xase complex inhibition

Abstract

Fucosylated glycosaminoglycan (FG), a structurally complex glycosaminoglycan found up to now exclusively in sea cucumbers, has distinct anticoagulant properties, notably a strong inhibitory activity of intrinsic factor Xase complex (FXase). Knowledge of the FG structures could facilitate the development of a clinically effective intrinsic FXase inhibitor for anticoagulant drugs. Here, a new fucosylated glycosaminoglycan was obtained from the widely traded sea cucumber <i>Bohadschia argus</i> The precise structure was deduced as {→4)-[l-Fuc3S4S-α-(1→3)-]-d-GlcA-β-(1→3)-d-GalNAc4S6S-β-(1} through analysis of its chemical properties and homogeneous oligosaccharides purified from its β-eliminative depolymerized products. The <i>B. argus</i> FG with mostly 3,4-di-<i>O</i>-sulfated fucoses expands our knowledge on FG structural types. This β-elimination process, producing oligosaccharides with well-defined structures, is a powerful tool for analyzing the structure of complex FGs. Among these oligosaccharides, an octasaccharide displayed potent FXase inhibitory activity. Compared with oligosaccharides with various degrees of polymerization (3<i>n</i> and 3<i>n</i> - 1), our analyses reveal that the purified octasaccharide is the minimum structural unit responsible for the potent selective FXase inhibition, because the d-talitol in the nonsaccharide is unnecessary. The octasaccharide with 2,4-di-<i>O</i>-sulfated fucoses is more potent than that of one with 3,4-di-<i>O</i>-sulfated fucoses. Thus, sulfation patterns can play an important role in the inhibition of intrinsic factor Xase complex.