Modified PF4 compositions and methods of use

Details Modified PF4 compositions and methods of use Modified PF4 compositions and methods of use

1989-07-06

1992-05-12

Moskowitz, Margaret

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

530327, 530380, A61K 702, A61K 3736, C07K 700, C07K 708

Patent

active

051129469

ABSTRACT:
The subject invention pertains to the use of modified PF4 and recombinant PF4(rPF4) as well as modified analogs (mutants) of PF4, and peptide fragments thereof, to inhibit angiogenesis. The modified PF4, analogs, and certain fragments are shown to have utility for treating angiogenic diseases and for the inhibition of endothelial cell proliferation. Also, the subject invention concerns modification of PF4 which facilitate the targeting of the biological activity of PF4 to specific locations.

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R. L. Lundblad and C. M. Noyes, Chemical Reagents for Protein Modification, vol. II, CRC Press (1984) pp. 123-139.
A. White and P. Handler and E. L. Smith, Principles of Biochemistry 5th Edition, McGraw Hill, New York (1973) pp. 804-805, 261.
Folkman, J., S. Taylor, C. Spillberg (1983) "The Role of Heparin in Angiogenesis," Ciba Found. Symp. 100:132-149.
Folkman, J., and M. Klagsbrun (1987) "Angiogenic factors," Science 235:442-447.
Folkman, J. (1984) Angiogenesis: Initiation and Modulation. In Cancer Invasion and Metastasis: Biologic and Therapeutic Aspects. G. L. Nicolson and L. Milas, eds. Raven Press, New York, pp. 201-208.
Taylor, S. and J. Folkman (1982) "Protamine is an inhibitor of angiogenesis," Nature 279:307-312.
Duel, T. F., P. S. Keim, M. Farmer, and R. L. Heinrikson (1977) "Amino acid sequence of human platelet factor 4," proc. Natl. Acad. Sci. U.S.A. 74(6):2256-2258.
Duel, T. F., R. M. Senior, D. Chang, G. L. Griffin, R. L. Heinrikson, and E. T. Kaiser (1981) "Platelet factor 4 is chemotactic for neutrophils and monocytes," Proc. Natl. Acad. Sci. U.S.A. 78:4585-4587.
Osterman, D. G., G. L. Griffin, R. M. Senior, E. T. Kaiser, and T. F. Deuel (1982) "The carboxyl-terminal tridecapeptide of platelet factor 4 is a potent chemotactic agent for monocytes," Biochem. and Biophys. Res. Comm. 107(1):130-135.

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