Heparin-like compounds prepared by chemical modification of capsular polysaccharide from E. coli K5.
O-Sulfation of sulfaminoheparosan SAH, a glycosaminoglucuronan with the structure-->4)-beta-D-GlcA(1-->4)-beta-D-GlcNSO3(-)-(1-->, obtained by N-deacetylation and N-sulfation of the capsular polysaccharide from E. coli K5, was investigated in order to characterize the sulfation pattern eliciting heparin-like activities. SAH was reacted (as the tributylammonium salt in N,N-dimethylformamide) with pyridine-sulfur trioxide under systematically different experimental conditions. The structure of O-sulfated products (SAHS), as determined by mono- and two-dimensional 1H and 13C NMR, varied with variation of reaction parameters. Sulfation of SAH preferentially occurred at O-6 of the GlcNSO3- residues. Further sulfation occurred either at O-3 or at O-2 of the GlcA residues, depending on the experimental conditions. Products with significantly high affinity for antithrombin and antifactor Xa activity were obtained under well-defined conditions. These products contained the trisulfated aminosugar GlcNSO3-3,6SO3-, which is a marker component of the pentasaccharide sequence through which heparin binds to antithrombin.
Casu
B
B
Istituto di Chimica e Biochimica G. Ronzoni, Milan, Italy.
Grazioli
G
G
Razi
N
N
Guerrini
M
M
Naggi
A
A
Torri
G
G
Oreste
P
P
Tursi
F
F
Zoppetti
G
G
Lindahl
U
U
D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D004926:Escherichia coli / Q000737:chemistry / Q000276:immunology*; D006493:Heparin; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008969:Molecular Sequence Data; D011135:Polysaccharides, Bacterial / Q000737:chemistry* / Q000302:isolation & purification; D013464:Sulfuric Acids / Q000032:analysis
D007202:Indicators and Reagents; D011135:Polysaccharides, Bacterial; D013464:Sulfuric Acids; D006493:Heparin