Preparation of chondroitin sulfate libraries containing disulfated disaccharide units and inhibition of thrombin by these chondroitin sulfates
| Autor: | Noriko Kusakabe, Hiroko Habuchi, Shiori Ohtake-Niimi, Kazuya Ishige, Osami Habuchi, Mario Numakura |
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| Rok vydání: | 2010 |
| Předmět: |
Sulfotransferase
Stereochemistry Disaccharide Disaccharides Biochemistry Antithrombins law.invention Small Molecule Libraries chemistry.chemical_compound Sulfation Thrombin law medicine Chondroitin Animals Humans Chondroitin sulfate Molecular Biology Dose-Response Relationship Drug Chondroitin Sulfates Fibrinogen Cell Biology In vitro chemistry Factor X Recombinant DNA Sulfotransferases medicine.drug |
| Zdroj: | Glycoconjugate journal. 27(5) |
| ISSN: | 1573-4986 |
| Popis: | Chondroitin sulfate (CS) containing GlcA-GalNAc(4,6-SO(4)) (E unit) and CS containing GlcA(2SO(4))-GalNAc(6SO(4)) (D unit) have been implicated in various physiological functions. However, it has been poorly understood how the structure and contents of disulfated disaccharide units in CS contribute to these functions. We prepared CS libraries containing E unit or D unit in various proportions by in vitro enzymatic reactions using recombinant GalNAc 4-sulfate 6-O-sulfotransferase and uronosyl 2-O-sulfotransferase, and examined their inhibitory activity toward thrombin. The in vitro sulfated CSs containing disulfated disaccharide units showed concentration-dependent direct inhibition of thrombin when the proportion of E unit or D unit in the CSs was above 15-17%. The CSs containing both E unit and D unit exhibited higher inhibitory activity toward thrombin than the CSs containing either E unit or D unit alone, if the proportion of the total disulfated disaccharide units of these CSs was comparable. The thrombin-catalyzed degradation of fibrinogen, a physiological substrate for thrombin, was also inhibited by the CS containing both E unit and D unit. These observations indicate that the enzymatically prepared CS libraries containing various amounts of disulfated disaccharide units appear to be useful for elucidating the physiological function of disulfated disaccharide units in CS. |
| Databáze: | OpenAIRE |
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