Human insulin-like growth factor analogs with reduced...

C - Chemistry – Metallurgy – 12 – N

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195/1.235, 195/1

C12N 15/18 (2006.01) A61K 38/30 (2006.01) C07K 14/65 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2007886

Synthetic genes encoding two 70-amino acid analogs of human insulin-like growth factor (hIGF-I) have been constructed and expressed in the yeast, Saccharomyces cerevisiae. The protein analogs, IGF 150 and IGF 125 contain the first 17 amino acids of the A chain of human insulin in place of residues 42 to 58 of hIGF-I, and residues 8-10 of the A chain in place of residues 49 to 51 of hIGF-I, respectively. The purified proteins have high affinity for the human type I IGF receptor (3.2 and 7.0 nM respectively) yet have reduced relative affinity for the human and murine 28 K IGF binding proteins (7 fold and 45 fold, respectively). IGF 150 is 100 times more active than normal hIGF-I in stimulating DNA synthesis in 3T3 cells, and should be a more active growth factor in vivo due to its reduced affinity for 28 K IGF binding proteins. The protein analogs thus have a variety of utilities such as in promoting lactation in animals; promoting growth and feed efficiency in animals; improving carcass quality by increasing lean and decreasing fat; promoting wound healing in animals, including humans; promoting glucose utilization in skeletal muscle, and stimulating erythropoiesis, the production of red blood cells.

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