1. Sulfated levan from Halomonas smyrnensis as a bioactive, heparin-mimetic glycan for cardiac tissue engineering applications.
- Author
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Erginer M, Akcay A, Coskunkan B, Morova T, Rende D, Bucak S, Baysal N, Ozisik R, Eroglu MS, Agirbasli M, and Toksoy Oner E
- Subjects
- Animals, Anticoagulants chemistry, Anticoagulants pharmacology, Biomimetic Materials chemistry, Biomimetic Materials pharmacology, Carbohydrate Conformation, Heart drug effects, Humans, Materials Testing, Mice, Molecular Dynamics Simulation, Thrombin antagonists & inhibitors, Fructans chemistry, Fructans pharmacology, Halomonas chemistry, Heparin metabolism, Myocardium cytology, Sulfates chemistry, Tissue Engineering
- Abstract
Chemical derivatives of levan from Halomonas smyrnensis AAD6(T) with low, medium and high levels of sulfation were synthesized and characterized by FTIR and 2D-NMR. Sulfated levan samples were found to exhibit anticoagulation activity via the intrinsic pathway like heparin in a dose-dependent manner. Exceptionally high heparin equivalent activity of levan sulfate was shown to proceed via thrombin inhibition where decreased Factor Xa activity with increasing concentration was observed in antithrombin tests and above a certain concentration, levan sulfate showed a better inhibitor activity than heparin. In vitro experimental results were then verified in silico by docking studies using equilibrium structures obtained by molecular dynamic simulations and results suggested a sulfation dependent binding mechanism. With its high biocompatibility and heparin mimetic activity, levan sulfate can be considered as a suitable functional biomaterial to design biologically active, functionalized, thin films and engineered smart scaffolds for cardiac tissue engineering applications., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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