ANTAGONISTS OF PARATHYROID HORMONE ACTION

这项拟议研究的目标是生产出有效的人类甲状旁腺。 激素(PTH)拮抗肽在大肠杆菌中的应用 最先进的重组DNA(RDNA)技术。临床实用价值 有效的甲状旁腺激素拮抗剂在体内的作用在于治疗 甲状旁腺素和甲状旁腺素样物质过度产生的高血钙性疾病 化合物。在微生物中产生甲状旁腺素拮抗剂多肽可能 比目前昂贵的生产方式在经济上更可行 使用化学合成。更重要的是，与传统的 化学合成，各种不同的类似物可以很容易地和 通过简单地改变拮抗者的基因而产生的经济 使用标准rDNA方法的多肽。因此，拟议的第一阶段 研究将确定一种类似于PTH拮抗剂的多肽 罗森布拉特和他的同事们所描述的 大量并有效地从大肠杆菌中纯化。这项工作对 需要大量PTH的第二阶段研究计划 用于广泛的动物和人体研究的拮抗肽。

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.