Anticoagulant and antithrombotic activities of modified xylofucan sulfate from the brown alga Punctaria plantaginea

Carbohydr Polym. 2016 Jan 20:136:826-33. doi: 10.1016/j.carbpol.2015.09.102. Epub 2015 Oct 1.

Abstract

Selectively and totally sulfated (1 → 3)-linked linear homofucans bearing ∼ 20 monosaccharide residues on average have been prepared from the branched xylofucan sulfate isolated from the brown alga Punctaria plantaginea. Anticoagulant and antithrombotic properties of the parent biopolymer and its derivatives were assessed in vitro. Highly sulfated linear fucan derivatives were shown to inhibit clot formation in APTT assay and ristocetin induced platelets aggregation, while the partially sulfated analogs were inactive. In the experiments with purified proteins, fucan derivatives with degree of sulfation of ∼ 2.0 were found to enhance thrombin and factor Xa inhibition by antithrombin III. The effect of sulfated fucans on thrombin inhibition, which was similar to those of heparinoid Clexane(®) (enoxaparin) and of a fucoidan from the brown alga Saccharina latissima studied previously, can be explained by the multicenter interaction and formation of a ternary complex thrombin-antithrombin III-polysaccharide. The possibility of such complexation was confirmed by computer docking study.

Keywords: Anticoagulant; Antithrombotic; Docking; Fucan sulfate; Punctaria plantaginea; Thrombin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anticoagulants / chemistry*
  • Anticoagulants / pharmacology
  • Blood Platelets / drug effects
  • Humans
  • Molecular Sequence Data
  • Phaeophyceae / chemistry
  • Plant Extracts / chemistry*
  • Plant Extracts / pharmacology
  • Platelet Aggregation Inhibitors / chemistry*
  • Platelet Aggregation Inhibitors / pharmacology
  • Polysaccharides / chemistry*
  • Polysaccharides / pharmacology
  • Protein Binding
  • Thrombin / chemistry
  • Thrombin / metabolism
  • Xylose / analogs & derivatives*
  • Xylose / chemistry

Substances

  • Anticoagulants
  • Plant Extracts
  • Platelet Aggregation Inhibitors
  • Polysaccharides
  • fucoidan
  • Xylose
  • Thrombin