Abstract
A covalently bound conjugate of commercial grade heparin and prostaglandin E1 (PGE,) was synthesized to provide the dual pharmacological role of decreasing the extent of platelet aggregation and inhibiting fibrin formation during thrombogenesis. The compound was synthesized using a modified mixed carbonic anhydride method of amide bond formation between the carboxylic acid moiety of PGE1, and a primary amine group on heparin. Quantitation of coupling was measured spectrophotometrically by monitoring a degradation product of the prostaglandin E1-heparin conjugate (prostaglandin B1-heparin conjugate). Bioactivity tests on the conjugates (activated partial throm-boplastin time and platelet aggregation) confirmed that both the anticoagulant activity of heparin and the inhibitory effect of PGE1 on platelet aggregation were maintained.
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