Chemokine N-terminal deletion mutations

Details Chemokine N-terminal deletion mutations Chemokine N-terminal deletion mutations

1996-07-16

1998-01-06

Degen, Nancy

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

Recombinant dna technique included in method of making a...

435 701, 4351721, 4353201, 435325, 536 231, 536 241, C12P 2102, C07H 2104, C12N 1585, C12N 1563

Patent

active

057053600

ABSTRACT:
The invention relates to mutant chemokines and pharmaceutical compositions thereof, wherein the mutant inhibits the corresponding endogenous chemokine from binding or activating a responsive receptor. The claimed mutant chemokines can be administered to a patient for the treatment or prophylaxis of a chemokine-mediated disease. The invention further relates to isolated DNAs encoding the mutant chemokines, vectors and recombinant host cells containing the same.

REFERENCES:
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Moser, B. et al., "Interleukin-8 Antagonists Generated by N-Terminal Modification," J. Biol. Chem., 268(10):7125-7128 (Apr. 1993).
Gong, J-H et al., "Antagonist of Monocyte Chemoattractant Protein-1 by Modification of the Functionally Critical N-terminal Residues," J. Exp. Med., 181:631-640 (Feb. 1995).
Rollins, Barrett et al., "Recombinant Human MCP-1/JE Induces Chemotaxis, Calcium Flux and Respiratory Burst in Human Monocytes," Blood, 78(4):1112-1116 (1991).
Prickett, K.S. et al., "A Calcium-dependent Antibody for Identification and Purification of Recombinant Proteins," Biotechniques, 7(6):580-589 (1989).
Koch, A.E. et al., "Enhanced production of chemotactic cytokines interleukin-8 and monocyte chemoattractant protein-1 in human abdominal aortic aneurysms," Am. J. Pathol., 142(s):1423-1431 (May 1993).
Schnitzel, Wolfgang et al., "Monomer-dimer equilibria of interleukin-8 and neutrophil-activating peptide 2. Evidence of IL-8 binding as a dimer and oligomer to IL-8 receptor B," J. Leukocyte Biol., 55:763-770 (1994).
Clark-Lewis, Ian et al., "Structure-activity relationships of chemokines," Journal of Leukocyte Biology, 57(5):703-711 (1995).
Gong, Jiang-Hong et al., "RANTES and MCP-3 Antagonists Bind Multiple Chemokine Receptors," Journal of Biological Chemistry, 271(18):10521-10527 (1996).
Zhang, Yujun and Rollins, Barrett J., "A Dominant Negative Inhibitor Indicates that Monocyte Chemoattractant Protein 1 Functions as a Dimer," Molecular and Cellular Biology, 15(9):3851-4855 (1995).

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