Human insulin-like growth factor analoges with reduced binding to serum carrier proteins and their production in yeast

摘要

A synthetic gene encoding a 71-amino acid analog of human insulin-like grouwth factor (hIGF-I) has been constructed and expressed in the yeast, Saccharomyces cerevisiae. The protein analog, IGF132, contains the first 17 amino acids of the B chain of human insulin in place of the first 16 amino acids of hIGF-I. The purified hybrid protein has high affinity for the type I IGF recepto (12 nM) yet has drastically reduced affinity for human serum carrier proteins ( 1000 nM). This analog is 5 to 10 times more active than normal hIGF-I in stimulating DNA synthesis in 3T3 cells and is a more active growth factor in vivo due to its reduced affinity for serum carrier proteins. Other proteins with similar properties have also been constructed. 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.