Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1994-10-27
1995-10-17
Beisner, William H.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 12, 514 21, 530351, 530395, 530402, 530409, 424 851, C07K 1452, C08H 100, A61K 3819, A61K 4505
Patent
active
054591287
ABSTRACT:
The invention relates to a human MCP-1 derivative, and pharmaceutical compositions thereof, wherein human MCP-1 has been modified such that the protein inhibits monocyte chemoattractant activity. Successful inhibition of the activity is found where the MCP-1 is modified in one or more of the following: a) the 28-tyrosine is substituted by aspartate, b) the 24-arginine is substituted by phenylalanine, c) the 3-aspartate is substituted by alanine, and/or d) the 2-8 amino acid sequence is deleted. The claimed MCP-1 derivatives can be administered to a patient in need of inhibiting MCP-1 monocyte chemoattractant activity. For example, the derivatives can be used to prevent restenosis, such as that which is common in a patient undergoing coronary artery angioplasty. The invention further relates to compositions and methods of inhibiting monocyte chemoattractant activity of MCP-1 employing the derivatives described.
REFERENCES:
patent: 5212073 (1993-05-01), Rollins et al.
patent: 5288711 (1994-02-01), Mitchell et al.
Koch, A. E. et al., "Enhanced Production of the Chemotactic Cytokines Interleukin-8 & Monocyte Chemoaltiactant Protein-1 in Human Aortic Aneurysms", Am. J. Pathol., 142(5), 1423-1431, May 1993.
Rollins, Barrett J. et al., "The Human Homolog of the JE Gene Encodes a Monocyte Secretory Protein", Molecular and Cellular Biology, 9(11):4687-4695, (1989).
Rollins, Barrett J. et al., "Recombinant Human MCP-1/JE Induces Chemotaxis, Calcium Flux, and the Respiratory Burst in Human Monocytes", Blood, 78(4):1112-1116, (1991).
Prickett, Biotechniques, 7:580-589, (1989).
Gronenborn, A. M. and Clore, G. M., "Modeling the three-dimensional structure of the monocyte chemo-attractant and activating protein MCAF/MCP-1 on the basis of the solution structure of interleukiin-8", Protein Eng., 4:263-269 (1991).
Beall, C. J., Mahajan, S. and Kolattukudy, P. E., "Conversion of monocyte chemoattractant protein-1 into a neutrophil attractant by substitution of two amino acids", J. Biol. Chem., 267:3455-3459 (1992).
Rollins Barrett
Zhang Yu J.
Beisner William H.
Dana-Farber Cancer Institute
Degen Nancy J.
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