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ECB-ART-46485
J Biol Chem 2018 Sep 07;29336:14089-14099. doi: 10.1074/jbc.RA118.003809.
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Oligosaccharides from depolymerized fucosylated glycosaminoglycan: Structures and minimum size for intrinsic factor Xase complex inhibition.

Yin R , Zhou L , Gao N , Li Z , Zhao L , Shang F , Wu M , Zhao J .


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 Bohadschia argus 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 B. argus FG with mostly 3,4-di-O-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 (3n and 3n - 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-O-sulfated fucoses is more potent than that of one with 3,4-di-O-sulfated fucoses. Thus, sulfation patterns can play an important role in the inhibition of intrinsic factor Xase complex.

PubMed ID: 30030375
PMC ID: PMC6130965
Article link: J Biol Chem


Genes referenced: LOC100887844

References [+] :
Casu, A conductimetric method for the determination of sulphate and carboxyl groups in heparin and other mucopolysaccharides. 1975, Pubmed