A series of covalent heparin-protein complexes with prolonged in vivo half lives of the heparin moiety and high anticoagulant activity will be developed. A series of proteins covering a broad range of molecular weights and isoelectric points will be chosen for these conjugates. Various conjugation techniques will be investigated to determine the method which will retain the best anticoagulant activity for the heparin. The relative ability of the covalent protein-heparin complexes to catalytically accelerate the inhibition of thrombin and factor X will be measured by stopped flow fluorimetry. Prolongation of activated partial thromboplastin time will be used to evaluate potential in vivo anticoagulant activity. Ultimately but not as part of the Phase I studies half lives and efficacy will be determined in controlled clinical studies.
