ANTAGONISTS OF PARATHYROID HORMONE ACTION

这项研究的目标是生产有效的人类甲状旁腺 激素（PTH）拮抗剂肽在大肠杆菌中使用 最先进的重组DNA（rDNA）技术。 的临床效用 体内PTH作用的有效拮抗剂在于治疗 涉及PTH和PTH样的过度产生的高钙症 化合物. 在微生物中生产PTH拮抗剂肽可以 比目前昂贵的生产方法更经济可行 使用化学合成。 更重要的是，与传统的 通过化学合成，可以容易地和 通过简单地改变拮抗剂的基因而经济地产生 使用标准rDNA方法对肽进行分析。 因此，拟议的第一阶段 研究将确定是否有类似的PTH拮抗肽， Rosenblatt及其同事所描述的， 并有效地从E.杆菌 这项工作对于 第二阶段研究计划将需要大量的PTH 拮抗肽用于广泛的动物和人类研究。

The goal of the proposed research is to produce effective human parathyroid hormone (PTH) antagonist peptides in Escherichia coli using state-of-the-art recombinant DNA (rDNA) technologies. The clinical utility of an effective antagonist to PTH action in vivo lies in the treatment of hypercalcemic disorders involving the overproduction of PTH and PTH-like compounds. The production of PTH antagonist peptides in microorganisms may be more economically feasible than the current costly method of production using chemical sythesis. More importantly, in contrast to conventional chemical synthesis, a variety of different analogues can be readily and economically produced by simply altering the gene for the antagonist peptide using standard rDNA methodologies. Therefore the proposed Phase I research will determine whether a PTH antagonist peptide similar to that described by Rosenblatt and colleagues can be produced in significant quantities and efficiently purified from E. coli. This work is critical to the Phase II research plan which will require significant quantities of PTH antagonist peptides for wide ranging animal and human studies.