EXPRESSION OF HUMAN RENIN FROM CLONED GENES

高血压是一个严重而普遍的医学问题。虽然种类繁多 在目前存在的控制高血压的方法中，许多患者 可能受益于新的降压药，这些药物比 那些目前可用的。肾素抑制剂是一类潜在的药物 一系列高效而特异的抗高血压药物。 设计有用的肾素抑制剂的一个障碍是缺乏 关于酶的结构的详细信息。纯人 肾素很难获得，到目前为止，还没有三维的 进行了结晶学分析。有人建议使用cDNA. 和编码人肾素的基因组克隆来生产这种酶 足以确定其晶体结构的数量。 提出了普罗瑞宁和成熟蛋白的合成方法。 哺乳动物细胞中的肾素和细菌中的成熟肾素。有建议说 在第一阶段，将进行适当的建造，并满足以下条件 将为获得所需的表达产品而建立。第二阶段 将包括酶的更大规模的生产和纯化。 大量纯人肾素的可获得性将使结构性 要进行的研究以及允许直接评估 新合成的肾素抑制剂的活性。

Hypertension is a serious and widespread medical problem. While a variety of approaches currently exist for controlling hypertension, many patients could benefit from new antihypertensive drugs that are more specific than those presently available. Renin inhibitors constitute a potential class of highly active yet specific antihypertensive agents. One impediment to the design of useful renin inhibitors is the lack of detailed information concerning the structure of the enzyme. Pure human renin is very difficult to obtain and as yet, no 3-dimensional crystallographic analysis has been performed. It is proposed to use cDNA and genomic clones coding for human renin to produce the enzyme in quantities sufficient for establishing its crystal structure. Constructions are proposed for the synthesis of both prorenin and mature renin in mammalian cells and for mature renin in bacteria. It is proposed that in Phase I, appropriate constructions will be made and that conditions will be established for obtaining the desired expressed products. Phase II will encompass the larger scale production and purification of the enzyme. The availability of large amounts of pure human renin will allow structural studies to be performed as well as allow for the direct assessment of the activity of newly synthesized renin inhibitors.