SELECTIVE INHIBITORS OF PLACENTAL STEROID AROMATASE

胎盘类固醇芳香酶的选择性抑制剂

• 批准号: 3311691
• 负责人: CECIL H ROBINSON
• 金额: $ 15.18万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-09-01 至 1994-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3311691
• 关键词: aromatase; chemical models; chemical structure function; drug design /synthesis /production; enzyme inhibitors; estrogen analog; estrogen inhibitor; hormone inhibitor; hormone metabolism; hormone regulation /control mechanism; human tissue; laboratory rat; ligase; placental hormones; steroid hormone

The objectives of this proposal include the design, synthesis an devaluation of specific inhibitors of human placental aromatase (estrogen synthetase). These inhibitors include enzyme-generated irreversible inhibitors and also competitive reversible inhibitors. Specific inhibitors of human biosynthesis in placental tissue and in other tissues. They may also be of value in the study and treatment of estrogen-dependent tumors, and in studying the role played by peripheral aromatization of androgen in male endocrinology. Mechanistic studies with these inhibitors should be of interest in further examination of the mechanism of action of aromatase. Covalent labeling of purified enzyme by radiolabeled inhibitors may provide valuable information about the enzyme's active site. A chemical model for aromatase has been developed, and this model will be evaluated in terms of the enzymatic process's stereochemical and kinetic behavior.

该方案的目标包括设计、综合和 人胎盘芳香酶特异性抑制物(雌激素)的贬值 合成酶)。这些抑制物包括酶产生的不可逆性 抑制剂和竞争性可逆抑制剂。特异性抑制剂 人类在胎盘组织和其他组织中的生物合成。他们可能会 对雌激素依赖型肿瘤的研究和治疗也有价值， 以及在研究雄激素的外周芳构化在 男性内分泌学。 对这些抑制剂的机理研究应该会有进一步的兴趣 芳香酶作用机理的研究。共价标记的研究进展 通过放射性标记抑制剂纯化的酶可能提供有价值的信息 关于这种酶的活性部位。芳香酶的化学模型已被提出 开发出来的，这个模型将根据酶 过程的立体化学和动力学行为。