Sulfation of some chemically-modified heparins. Formation of a 3-sulfate analog of heparin.
A modified form of heparin containing residues of nonsulfated alpha-L-idopyranosyluronic acid (7) in place of the normal 2-sulfate (1) was sulfated with sulfur trioxide-trimethylamine in dimethylformamide at 0 and 25 degrees. Examination of the reaction products by n.m.r. spectroscopy showed that sulfation occurred selectively at C-3 of residue 7, to give a new polymer that may be described as a 3-sulfate analog of heparin. A slower substitution reaction led subsequently to sulfation at C-3 of 2-deoxy-2-sulfamino-alpha-D-glucopyranosyl 6-sulfate residues (2), although this was accompanied by partial N-desulfation of 2. An analogous pattern of O-sulfation-N-desulfation was observed for the residues of 2 in two other modified heparins, one containing residues of 2,3-anhydro-alpha-L-gulopyranosyluronic acid and the other residues of alpha-L-galactopyranosyluronic acid, in place of residues of 1. The galacto diastereomer exhibited relatively low regioselectivity, as it was found to be sulfated at C-2 or C-2.3, or both. Selective resulfation of free amino groups gave the products that were examined for anticoagulant activity and susceptibility to enzymolysis by heparinase. Antithrombin-binding affinity measurements were also carried out. Although none of the materials had significant anti-Xa activity, nor were they affected by heparinase, their patterns of binding to antithrombinagarose were not dissimilar to that of heparin.
Rej
R N
RN
Department of Chemistry, McGill University, Montreal, Canada.
Ludwig-Baxter
K G
KG
Perlin
A S
AS
D000925:Anticoagulants / Q000138:chemical synthesis*; D000991:Antithrombins / Q000378:metabolism; D002240:Carbohydrate Sequence; D006493:Heparin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D019763:Heparin Lyase; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011133:Polysaccharide-Lyases / Q000378:metabolism; D013464:Sulfuric Acids / Q000138:chemical synthesis / Q000378:metabolism
D000925:Anticoagulants; D000991:Antithrombins; D013464:Sulfuric Acids; D006493:Heparin; D011133:Polysaccharide-Lyases; D019763:Heparin Lyase