Ustyuzhanina NE et al. (2020), Fucosylated Chondroitin Sulfates from the Sea C...

ECB-ART-49519

Mar Drugs 2020 Oct 28;1811:. doi: 10.3390/md18110540.

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Fucosylated Chondroitin Sulfates from the Sea Cucumbers Paracaudina chilensis and Holothuria hilla: Structures and Anticoagulant Activity.

Ustyuzhanina NE , Bilan MI , Dmitrenok AS , Silchenko AS , Grebnev BB , Stonik VA , Nifantiev NE , Usov AI .

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Fucosylated chondroitin sulfates (FCSs) PC and HH were isolated from the sea cucumbers Paracaudina chilensis and Holothuria hilla, respectively. The purification of the polysaccharides was carried out by anion-exchange chromatography on a DEAE-Sephacel column. The structural characterization of the polysaccharides was performed in terms of monosaccharide and sulfate content, as well as using a series of nondestructive NMR spectroscopic methods. Both polysaccharides were shown to contain a chondroitin core [→3)-β-d-GalNAc (N-acethyl galactosamine)-(1→4)-β-d-GlcA (glucuronic acid)-(1→]n, bearing sulfated fucosyl branches at O-3 of every GlcA residue in the chain. These fucosyl residues were different in their pattern of sulfation: PC contained Fuc2S4S and Fuc4S in a ratio of 2:1, whereas HH included Fuc2S4S, Fuc3S4S, and Fuc4S in a ratio of 1.5:1:1. Moreover, some GalNAc residues in HH were found to contain an unusual disaccharide branch Fuc4S-(1→2)-Fuc3S4S-(1→ at O-6. Sulfated GalNAc4S6S and GalNAc4S units were found in a ratio of 3:2 in PC and 2:1 in HH. Both polysaccharides demonstrated significant anticoagulant activity in a clotting time assay, which is connected with the ability of these FCSs to potentiate the inhibition of thrombin and factor Xa in the presence of anti-thrombin III (ATIII) and with the direct inhibition of thrombin in the absence of any cofactors.

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	Figure 1. The 13C NMR spectra of the fucosylated chondroitin sulfates PC and HH.
	Figure 2. Fragments of 1H NMR spectra of the fucosylated chondroitin sulfates PC and HH.
	Figure 3. Repeating blocks of fucosylated chondroitin sulfates PC (units A–D, F) and HH (units A–J). Unit A bears Fuc2S4S (D), whereas unit A’ bears Fuc3S4S (E) or Fuc4S (F).
	Figure 4. The HSQC NMR spectra of polysaccharides PC (A) and HH (B).
	Figure 5. Anticoagulant activity of polysaccharides PC (blue), HH (red), CD (orange), heparin (black), and enoxaparin (dotted line). (A) Activate partial thromboplastin time (APTT) assay, (B) anti-IIa-activity in the presence of antithrombin III (ATIII), (C) anti-Xa-activity in the presence of ATIII, and (D) anti-IIa-activity without ATIII. n = 4, p < 0.05.