人生长激素突变体的制备及其对受体亲和力和生物活性的研究  

PREPARATION OF HUMAN GROWTH HORMONE MUTANTS AND STUDIES ON ITS RECEPTOR BINDING ABILITIES AND BIOLOGICAL ACTIVITIES

作　　者：李伟[1] 朱丽华[1] 汪恩壁[1] 徐燕萍[1] 姜晓东[1] 郭礼和[1] 

机构地区：[1]中国科学院上海生命科学研究院生物化学与细胞生物学研究所,上海200031

出　　处：《细胞生物学杂志》2003年第1期52-55,共4页Chinese Journal of Cell Biology

摘　　要：本文采用DNA重组技术制备了三种重组人生长激素(recombinant human growthhormone,rhGH)突变体,并测定了其受体亲和力及对去垂体大鼠的促体重增加活力。实验结果显示其受体亲和力大小依次为:rhGH-E174A>rhGH-G120R>rhGH>rhGH-G120T。 rhGH-G120R和rhGH-G120T二种突变体相比rhGH来说,对去垂体大鼠促体重增加生物活性明显降低;rhGH-E174A突变体则完全丧失生物活性。由于rhGH-E174A的受体亲和办高于rhGH,表明它是一种较强的hGH拮抗剂,可能成为一种药物,在临床上用于治疗因hGH分泌过多而引起的疾病(例如巨人症,肢端肥大症等)。Three recombinant human growth hormone hGH mutants, rhGH-G120T, rhGH-E174A and rhGH-G120R,were constructed and expressed in E. coli. . Their receptor binding activities were evaluated with their abilities to inhibit the binding of 125I-hGH to growth hormone receptor on the membrane of pregnant rabbit liver cells. The results showed that the order of their receptor binding activities was:rhGH-E174A>rh-GH-G120R>rhGH>rhGH-G120T. rhGH-G120T and rhGH-G120R had lower biological activities to promote the body weight gain in hypophysectomized rat than rhGH, but rhGH-E174A mutant did not have any biological activity to promote the body weight gain in hypophysectomized rat. Therefore, rhGH-E174A is likely to be a good candidate for hGH antagonist.

关 键 词：人生长激素突变体 制备 生物活性 拮抗剂 受体亲和力 

分 类 号：R346[医药卫生—基础医学]