Analogs of hirudin

Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 25 or more amino acid residues in defined sequence

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530350, 530816, 530813, 530812, 530811, C07K 708

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active

060281707

ABSTRACT:
A tyrosine-substituted hirudin analog has antithrombogenic activity. Further simultaneous reaction at native tyrosine residues is prevented by mutation at those sites to encode nonreactive amino acids. Several novel strategies for coupling the hirudin analog to solid surfaces while simultaneously conserving antithrombogenic activity are disclosed.

REFERENCES:
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patent: 4767742 (1988-08-01), Dodt et al.
patent: 4791100 (1988-12-01), Kramer et al.
patent: 4801576 (1989-01-01), Fritz et al.
DiMaio, J. et al., "Bifunctional Thrombin Inhibtors Based on the Sequence of Hirudin," J. Biol. Chem., vol. 265, No. 35, pp. 21698-21703 (1990).
Johnson, P. H. et al., "Biochemistry and Genetic Engineering of Hirudin," Seminars in Thrombosis and Hemostasis, vol. 15, No. 3, 1989.
Lazar, J. B. et al., "Hirudin:Amino-Terminal Residues Play a Major Role in the Interaction with Thrombin," J. Biol. Chem., vol. 266, No. 2 pp. 685-688 (1991).
Maraganore, J. M. et al., "Design and Characterization of Hirulogs:A Novel Class of Bivalent Peptide," Abstract presented symposium "Biomedical Horizons of the Leech," Oct. 24-28, 1990.
Maraganore, J. M., et al., "Design and Characterization of Hirulogs:A Novel Class of Bivalent Peptide Inhibitors of Thrombin," Biochemistry 29, pp. 7095-7101 (1990).
Markwardt, F. "Development of Hirudin as an Antithrombotic Agent," Seminars in Thrombosis and Hemostatis, vol. 15, No. 3, pp. 269-282 (1989).
Rydel, T. J. et al., "The Structure of a Complex of Recombinant Hirudin and Human Antithrombin," Science, 249, pp. 277-280 (1990).
Krstenansky, J.L. et al., J. Med. Chem. 30, pp. 1688 to 1691 (1987).

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