Regioselectivity in the sulfation of some chemically-modified heparins, and observations on their cation-binding characteristics.
Two modified forms of heparin, polymers A and B, have been prepared, one containing residues of nonsulfated alpha-L-idopyranosyluronic acid (3) and the other residues of alpha-L-galactopyranosyluronic acid (7), in place of the normal alpha-L-idopyranosyluronic acid 2-sulfate (1). In addition, both A and B contained 2-acetamido-2-deoxy-alpha-D-glucopyranosyl 6-sulfate residues (6) in place of the corresponding N-sulfated residues (2) of the original heparin. These polymers were subjected to sulfation under various conditions. Examination of the products by NMR spectroscopy showed that polymer A was sulfated initially at position-3 of residue 3, and that slower substitution occurred at position-3 of 6. By contrast, polymer B exhibited low regioselectivity, as sulfation occurred with about equal facility at positions-2 and -3 of 7, and -3 of 6. The sulfation products had no significant anti Xa activity. Based on the paramagnetic effects of Cu2+ and chemical shift displacements induced by Ca2+, NMR spectroscopy was used to compare cation-binding properties of A and B with those of heparin. In contrast to heparin, which forms a complex with Cu2+ detectable at a level of < 10(-3) mol per dimeric unit of the polymer, neither A nor B exhibited an interaction with the cation. However, polymer A was found to bind Ca2+, in this respect being distinct from the related modification, 1-->6, which contains a 2-sulfate group in 1, as well as from polymer B.
Liu
Z
Z
Department of Chemistry, McGill University, Montreal, Quebec, Canada.
Perlin
A S
AS
D002240:Carbohydrate Sequence; D002412:Cations / Q000378:metabolism*; D006493:Heparin / Q000737:chemistry*; D008969:Molecular Sequence Data; D013431:Sulfates / Q000378:metabolism*; D014574:Uronic Acids / Q000737:chemistry*
D002412:Cations; D013431:Sulfates; D014574:Uronic Acids; D006493:Heparin