Preparation and Characterization of O-Acylated Fucosylated Chondroitin Sulfate from Sea Cucumber

Fucosylated chondroitin sulfate (FuCS), a kind of complex glycosaminoglycan from sea cucumber, has potent anticoagulant activity. In order to understand the relationship between structures and activity, the depolymerized FuCS (dFuCS) was chosen to prepare its derivates by selective substitution at OH groups. Its O-acylation was carried out in a homogeneous way using carboxylic acid anhydrides. The structures of O-acylated derivatives were characterized by NMR. The results indicated that the 4-O-sulfated fucose residues may be easier to be acylated than the other ones in the sulfated fucose branches. But the O-acylation was always accompanied by the β-elimination, and the degree of elimination was higher as that of acylation was higher. The results of clotting assay indicated that the effect of partial O-acylation of the dFuCS on their anticoagulant potency was not significant and the O-acylation of 2-OH groups of 4-O-sulfated fucose units did not affect the anticoagulant activity.

[1]  Jinhua Zhao,et al.  Structure and effect of sulfated fucose branches on anticoagulant activity of the fucosylated chondroitin sulfate from sea cucumber Thelenata ananas. , 2012, Carbohydrate polymers.

[2]  P. Amodeo,et al.  Chemical modification of pectin : environmental friendly process for new potential material development , 2011 .

[3]  Jinhua Zhao,et al.  Physicochemical characteristics and anticoagulant activities of low molecular weight fractions by free-radical depolymerization of a fucosylated chondroitin sulphate from sea cucumber Thelenata ananas , 2010 .

[4]  C. Takiya,et al.  Fucosylated chondroitin sulfate attenuates renal fibrosis in animals submitted to unilateral ureteral obstruction: a P-selectin-mediated event? , 2010, American journal of physiology. Renal physiology.

[5]  Jinhua Zhao,et al.  Free-radical depolymerization of glycosaminoglycan from sea cucumber Thelenata ananas by hydrogen peroxide and copper ions , 2010 .

[6]  J. Sheehan,et al.  Fucosylated chondroitin sulfate inhibits plasma thrombin generation via targeting of the factor IXa heparin-binding exosite. , 2009, Blood.

[7]  P. A. Mourão,et al.  Serpin-independent anticoagulant activity of a fucosylated chondroitin sulfate , 2008, Thrombosis and Haemostasis.

[8]  A. Sakakura,et al.  Widely useful DMAP-catalyzed esterification under auxiliary base- and solvent-free conditions. , 2007, Journal of the American Chemical Society.

[9]  E. Atkins.  Conformations in polysaccharides and complex carbohydrates , 1985, Journal of Biosciences.

[10]  J. Sheehan,et al.  Depolymerized holothurian glycosaminoglycan and heparin inhibit the intrinsic tenase complex by a common antithrombin-independent mechanism. , 2005, Blood.

[11]  Yun Jiang,et al.  Synthesis and NMR structural analysis of O-succinyl derivative of low-molecular-weight κ-carrageenan , 2005 .

[12]  H. Mayr,et al.  The DMAP-catalyzed acetylation of alcohols--a mechanistic study (DMAP = 4-(dimethylamino)pyridine). , 2005, Chemistry.

[13]  A. Valente,et al.  Sulfated Fucans from the Egg Jellies of the Closely Related Sea Urchins Strongylocentrotus droebachiensis and Strongylocentrotus pallidus Ensure Species-specific Fertilization* , 2002, The Journal of Biological Chemistry.

[14]  Y. Nakagawa,et al.  Preparation of O-acylated low-molecular-weight carrageenans with potent anti-HIV activity and low anticoagulant effect , 2000 .

[15]  B. Mulloy,et al.  Structure and Anticoagulant Activity of a Fucosylated Chondroitin Sulfate from Echinoderm , 1996, The Journal of Biological Chemistry.

[16]  E. De Clercq,et al.  Preparation and anti-HIV activity of O-acylated heparin and dermatan sulfate derivatives with low anticoagulant effect. , 1993, Journal of medicinal chemistry.

[17]  C. Simenel,et al.  Selectively O-acylated glycosaminoglycan derivatives , 1992 .

[18]  K. Numata,et al.  Structure of DHG, a depolymerized glycosaminoglycan from sea cucumber, Stichopus japonicus , 1992 .

[19]  B. Mulloy,et al.  Structure of a fucose-branched chondroitin sulfate from sea cucumber. Evidence for the presence of 3-O-sulfo-beta-D-glucuronosyl residues. , 1991, The Journal of biological chemistry.

[20]  E. Lian,et al.  Aggregation of Human Platelets by Acidic Mucopolysaccharide Extracted from Stichopus japonicus Selenka , 1988, Thrombosis and Haemostasis.

[21]  J. Kiss.  β-Eliminative Degradation of Carbohydrates Containing Uronic Acid Residues , 1974 .