Du Hai-Juan, Shi Jia-Hao, Cui Da-Fu, Zhang You-Shang
Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Acta Biochim Biophys Sin (Shanghai). 2006 Aug;38(8):537-42. doi: 10.1111/j.1745-7270.2006.00198.x.
Studies on monomeric insulin with reduced self-association are important in the development of insulin pharmaceutical preparations with rapid hypoglycemic action on patients with diabetes. Here we report a novel monomeric insulin, B22 Glu des-B30 insulin, prepared from a single chain insulin precursor with B22 Arg mutated to Glu, which was expressed in Pichia pastoris and converted to B22 Glu des-B30 insulin by tryptic digestion. It still retains 50% of the in vivo biological activity of porcine insulin and does not form a dimer even at a concentration of 10 mg/ml, showing that B22 Glu plays a key role in reducing the self-association of the insulin molecule without greatly reducing its biological activity. This novel monomeric insulin might have potential applications in the clinic.
对具有降低的自我缔合能力的单体胰岛素的研究，对于开发对糖尿病患者具有快速降血糖作用的胰岛素药物制剂具有重要意义。在此，我们报告一种新型单体胰岛素，即B22 Glu去B30胰岛素，它由B22精氨酸突变为谷氨酸的单链胰岛素前体制备而成，该前体在毕赤酵母中表达，并通过胰蛋白酶消化转化为B22 Glu去B30胰岛素。它仍保留猪胰岛素50%的体内生物活性，即使在浓度为10 mg/ml时也不会形成二聚体，这表明B22 Glu在降低胰岛素分子的自我缔合方面起着关键作用，而不会大幅降低其生物活性。这种新型单体胰岛素可能在临床上具有潜在应用价值。
