Recombinant protein S variants deficient in C4BP binding activit

Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Blood proteins or globulins – e.g. – proteoglycans – platelet...

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530830, 435 696, 4351723, C07K 1300, C12N 1512

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active

054059461

ABSTRACT:
The present invention describes a variant protein S protein that is substantially homologous in amino acid residue sequence to wild-type mature human protein S, which has in vitro anticoagulant activity and has a reduced ability to bind C4b binding protein (C4BP), compositions containing the variant protein S, and recombinant DNA vectors for expressing the variant protein. Also disclosed are therapeutic methods of using variant protein S for inhibiting thrombosis, inflammation and the like conditions ameliorated by protein S.

REFERENCES:
Chang, et al., "The Carboxy Terminal Loop of Human Protein S is involved in the Interaction with Human C4b-Binding Protein", Blood, vol. 78, Supp. 1: Abstr. 1099, p. 277a (1991).
Chang, et al., "Characterization of Thrombin-Resistant Variants of Recobinant Human Protein S", Circulation, vol. 86, Supp. 1: Abstr. 3241 (1992).
Chang, et al., "Expression and Characterization of Recombinant Human Protein S in Heterologous Cells-Studies of the Interaction of Amino Acid Residues Leu-608 to Glu-612 with Human C4b-Binding Protein", Thromb. Haemost., 67:526-532 (1992).
DiScipio and Davie, "Characterization of Protein S, a .gamma.-Carboxyglutamic Acid Containing Protein from Bovine and Human Plasma", Biochem, 18: 899-904 (1979).
Fernandez and Griffin, "Identification of Regions of Protein S Essential For Binding To C4b-Binding Protein", Thromb. Haemost., vol. 65, Supp.: Abstr. 196, p. 711 (1991).
Griffin, et al., "Reevaluation of Total, Free, and Bound Protein S and C4b-Binding Protein Levels in Plasma Anticoagulated with Citrate or Hirudin", Blood, 79: 3203-3211 (1992).
Lundwall, et al., "Isolation and Sequence of the cDNA for Human Protein S, a Regulator of Blood Coagulation", Proc. Natl. Acad. Sci. USA, 83: 6716-6720 (1986).
Taylor, et al., "C4b-Binding Protein Exacerbates the Host Response to Escherichia Coli", Blood, 78: 357-363 (1991).

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