Keutmann H T, Griscom A W, Nussbaum S R, Reiner B F, Goud A N, Potts J T, Rosenblatt M
Endocrinology. 1985 Sep;117(3):1230-4. doi: 10.1210/endo-117-3-1230.
The rat PTH molecule contains five sequence differences from either the bovine or the human hormone within the biologically active 1-34 region. A synthetic rat 1-34 peptide was tested for activity by in vitro activation of canine and rat renal adenylate cyclase and binding to canine renal membrane receptors. The mean potency of 21,400 Medical Research Council units/mg in the canine adenylate cyclase system and 24,900 in the rat system was 8- to 10-fold higher than human 1-34 and 2- to 4-fold greater than bovine 1-34. These values represent the highest potency we have observed to date for a PTH preparation by these assay systems. In contrast, receptor binding of the rat fragment was comparable to that of bovine and human 1-34. Half-maximal inhibition of radioligand binding occurred at 1.7- 2.0 X 10(-9) M with all synthetic hormones. Hence, the amino acid substitutions in rat 1-34 appear to affect the cyclase-activating sequence domain without increasing avidity for the receptor. Analogs combining the rat sequence with modifications known to enhance receptor binding and/or retard enzymatic degradation offer a promising approach to the preparation of still more potent parathyroid agonists.
大鼠甲状旁腺激素（PTH）分子在生物活性1 - 34区域内与牛或人激素相比有五个序列差异。通过体外激活犬和大鼠肾腺苷酸环化酶以及与犬肾膜受体结合来测试合成的大鼠1 - 34肽的活性。在犬腺苷酸环化酶系统中，其平均效力为21,400医学研究委员会单位/毫克，在大鼠系统中为24,900，比人1 - 34高8至10倍，比牛1 - 34高2至4倍。这些值代表了我们迄今为止通过这些测定系统观察到的PTH制剂的最高效力。相比之下，大鼠片段的受体结合与牛和人1 - 34的相当。所有合成激素在1.7 - 2.0×10（-9）M时出现放射性配体结合的半数最大抑制。因此，大鼠1 - 34中的氨基酸取代似乎影响环化酶激活序列结构域，而不会增加对受体的亲和力。将大鼠序列与已知可增强受体结合和/或延缓酶降解的修饰相结合的类似物，为制备更有效的甲状旁腺激动剂提供了一种有前景的方法。
