Human monocyte chemoattractant protein-1 (mcp-1) derivatives

Details Human monocyte chemoattractant protein-1 (mcp-1) derivatives Human monocyte chemoattractant protein-1 (mcp-1) derivatives

C - Chemistry, Metallurgy

12

N

C12N 15/19 (2006.01) A61K 38/19 (2006.01) C07K 14/52 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2176217

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 restinosis, 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.

Dérivé de MCP-1 humaine, et compositions pharmaceutiques le contenant, dans lesquelles la MCP-1 humaine est modifiée de telle sorte que la protéine inhibe l'activité chimiotactique monocytaire. On trouve une inhibition efficace de cette activité là où la MCP-1 a subi une ou plusieurs des modifications suivantes: (a) la tyrosine 28 est substituée par aspartate, (b) l'arginine 24 est substituée par phénylalanine, (c) laspartate 3 est substitué par alanine, et/ou (d) la séquence d'acides aminés 2-8 est supprimée. On peut administrer les dérivés de MCP-1 revendiqués à un malade ayant besoin d'une inhibition de l'activité chimiotactique monocytaire de MCP-1. On peut par exemple utiliser les dérivés dans la prévention d'une resténose telle que celle qui survient fréquemment chez les malades subissant une angioplastie de l'artère coronaire. On a également prévu des compositions et des procédés d'inhibition de l'activité chimiotactique monocytaire de MCP-1 à l'aide des dérivés précités.

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