Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 161, Issue -, Pages 1552-1558Publisher
ELSEVIER
DOI: 10.1016/j.ijbiomac.2020.08.069
Keywords
Anticoagulant; Acylated chitosan sulfate; Antithrombin III
Funding
- Pukyong National University Research Fund
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Acylated chitosan sulfate (ChS1), a sulfated polysaccharide with high anticoagulant activity, was chemically synthesized and structurally characterized using FT-IR analysis. The beneficial structural properties and high availability of the sulfate group in ChS1 led to greater anticoagulant activity through both the intrinsic and common pathways with antithrombin III (AT III)-mediated inhibition, particularly involving coagulation factors FXa and FIIa. The analysis of the binding affinities using surface plasma resonance found that the equilibrium dissociation constant (K-D) of ChS1 for FXa and FIIa in the presence of AT III was 67.4 nM and 112.6 nM, respectively, indicating the stronger interaction of the AT III/ChS1 complex with the ligands and the inhibition of activated FX and FII. The results of amidolytic assays further demonstrated the stronger inhibition of the proteolytic conversion of factor X by the intrinsic FXase complex and of FII by the prothrombinase complex. Molecular docking analysis further validated the protein-ligand interactions of ChS1 with AT III and their binding affinity. (c) 2020 Elsevier B.V. All rights reserved.
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