Effect of 6-O-sulfonate hexosamine residue on anticoagulant activity of fully O-sulfonated glycosaminoglycans.
Intact and fully O-sulfonated glycosaminoglycans (GAGs) including chondroitin sulfate, dermatan sulfate, hyaluronan, heparan sulfate and heparin were chemically de-O-sulfonated on their hexosamine C-6 position (6-O-desulfonation) using N,O-bis(trimethylsilyl) acetamide. 1H NMR spectroscopy and chemical compositional analysis showed that the chemical de-O-sulfonation at C-6 position of hexosamine residues in both intact and fully O-sulfonated GAGs was completely achieved. Since GAGs and their derivatives are often used as anticoagulant agents, their anti-amidolytic activities were determined. While most of anticoagulant activity of fully O-sulfonated GAGs (FGAGs) and heparin disappeared following chemical 6-O-desulfonation, the activity of 6-O-desulfonated fully O-sulfonated dermatan sulfate (De6FDS) remained. This observation suggests the importance of the position of O-sulfonate groups for anti-coagulant activity.
Toida
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T
Faculty of Pharmaceutical Sciences, Chiba University, Inage, Japan.
Suzuki
A
A
Nakajima
K
K
Chaidedgumjorn
A
A
Imanari
T
T
D000925:Anticoagulants / Q000737:chemistry* / Q000494:pharmacology*; D065427:Factor Xa Inhibitors; D006025:Glycosaminoglycans / Q000737:chemistry* / Q000494:pharmacology*; D006031:Glycosylation; D006801:Humans; D007096:Imidoesters; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D011516:Prothrombin / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D013451:Sulfonic Acids / Q000737:chemistry; D014297:Trimethylsilyl Compounds
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D006025:Glycosaminoglycans; D007096:Imidoesters; D013451:Sulfonic Acids; D014297:Trimethylsilyl Compounds; C080718:N,O-bis(trimethylsilyl)acetamide; D011516:Prothrombin; C025337:Factor IIa