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MODE OF ACTION & SYNTHESIS OF PROGESTATIONAL HORMONES

行动方式

基本信息

批准号：
3224663
负责人：
HILTON A SALHANICK
金额：
$ 12.45万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
1977
资助国家：
美国
起止时间：
1977-04-01 至 1987-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3224663
关键词：
adrenocorticotropic hormone aminoglutethimide chemical cleavage corpus luteum cytochrome P450 heme hormone inhibitor hormone regulation /control mechanism human subject menstrual cycle pituitary gonadal axis pregnenolone progesterone spectrometry steroid hormone biosynthesis

项目摘要

This proposal deals with the synthesis of pregnenolone, the precursor to progesterone and its inhibition in vitro and in vivo. The in vitro studies will involve the purification and characterization of corpus luteum cytochrome P-450. The interactions at the active site will be studied by equilibrium binding, optic and paramagnetic spectral techniques with radioactive and spin-labeled substrate and inhibitor analogs. Other studies will deal with the target effects of the progesterone molecule including its binding energies and those of monosubstituted congeners. Appropriate substances of potential pharmacologic significance will be assessed further by bioassay. Purification of placental aromatase will also be undertaken and characteristics of the purified protein and its substrate and inhibitor sites will be studied.

该建议涉及合成双烯醇酮，双烯醇酮的前体，孕酮及其在体外和体内的抑制。体外研究将涉及黄体细胞色素P-450的纯化和表征。将通过平衡结合研究活性位点的相互作用，光学和顺磁光谱技术与放射性和自旋标记底物和抑制剂类似物。其他研究将涉及目标孕酮分子的影响，包括其结合能和单取代同系物。潜在药理学的适当物质将通过生物测定进一步评估显著性。胎盘纯化芳香酶也将进行，纯化蛋白质的特征并对其底物和抑制剂位点进行研究。