Gao N et al. (2012), Preparation and characterization of O-acylated ...

ECB-ART-42587

Mar Drugs 2012 Aug 01;108:1647-1661. doi: 10.3390/md10081647.

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Preparation and characterization of O-acylated fucosylated chondroitin sulfate from sea cucumber.

Gao N , Wu M , Liu S , Lian W , Li Z , Zhao J .

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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.

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Genes referenced: LOC100887844

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References [+] :

Buyue, Fucosylated chondroitin sulfate inhibits plasma thrombin generation via targeting of the factor IXa heparin-binding exosite. 2009, Pubmed

	Figure 1. 1H and 13C NMR spectra of the original dFuCS (B, E) and its different acylated degrees of O-propionyl derivatives (C, F, 40%; D, G, 95%). Chemical shifts are relative to external trimethylsilyl propionic acid at 0 ppm. The Panel A shows the structural units of the fucosylated chondroitin sulfate and its derivatives. Signals designate by “Fuc2S4S”, “Fuc3S”, “Fuc4S”, “A” and “GlcUA, or U” refer to those produced by 2,4-disulfated-fucose,3-sulfated-fucose, 4-sulfated-fucose residues, N-acetyl-β-D-galactosamin and β-D-glucuronic acid respectively. Then ΔU is α,β-unsaturated glucuronic acid residues. The legend a and b stands for the peaks of methyene and methyl group in the propionyl group respectively.
	Figure 2. Part of 1H NMR of the O-acetyl fucosylated chondroitin sulfate (A), O-succinic acyl dFuCS (B) and O-propionyl dFuCS (C).
	Figure 3. Proposed mechanism of the DMAP-catalyzed acylation of the fucosylated chondroitin sulfate.
	Figure 4. UV spectra of dFuCS (A), O-succinoyl (B), O-propionoyl (C, 40%; E, 84%), and O-acetyl (D) derivatives.
	Figure 5. 1H-1H COSY spectra of the dFuCS (A), its O-propionoyl derivativesdFuCS-P40 (degree of acylation, 40%) (B), and dFuCS-P95 (degree of acylation, 95%) (C), signals designate by “GalNAc4S6S” and “GlcUA” refer to those produced by 4,6-disulfated-acetyl-galactosamine, and β-D-glucuronic acid, respectively; whereas those of their corresponding O-acylated derivatives are labeled “Fuc2S3Pr4S”, “Fuc2S4Pr”, “Fuc2Pr3S4Pr”, “Fuc2Pr3S”, “Fuc2Pr4S” and “GlcUA2Pr”, respectively. Then ΔU, and ΔUA2Pr are the two kinds of α,β-unsaturated glucuronic acid residues.
	Figure 6. Effect of acylation on the anticoagulant activity.