Evidence of a selective free radical degradation of heparin, mediated by cupric ion.
A free radical reaction generated by a mixture of Cu2+, hydrogen peroxide, and ascorbate causes an abrupt reduction in the anti Xa activity of heparin by about one-half, and in molecular weight by about one-third. The product, which has the characteristics of a "low molecular weight" heparin, differs little in constitution from the intact heparin, on the basis of NMR evidence that includes data for fractions of the polymers. The free radical attack appears to occur adjacent to, rather than directly upon, some residues of alpha-L-iduronic acid 2-sulfate. Substitution of the Cu2+ with Fe2+, results in a less selective alteration of the heparin. Dermatan sulfate undergoes more extensive degradation than heparin with the Cu-reagent, although its anti Xa a potency is less drastically reduced. Overall, the results are more consistent with a high degree of regioselectivity in the interaction between heparin and Cu2+ ion, than with a delocalized counter-ion interaction.
Liu
Z
Z
Department of Chemistry, McGill University, Montreal, PQ, Canada.
Perlin
A S
AS
D001205:Ascorbic Acid / Q000737:chemistry; D002240:Carbohydrate Sequence; D003300:Copper / Q000737:chemistry; D003871:Dermatan Sulfate / Q000737:chemistry; D065427:Factor Xa Inhibitors; D005609:Free Radicals; D006493:Heparin / Q000737:chemistry* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data
D065427:Factor Xa Inhibitors; D005609:Free Radicals; D003871:Dermatan Sulfate; D003300:Copper; D006493:Heparin; D001205:Ascorbic Acid