SYNTHESIS AND PURIFICATION OF BIOLOGICALLY IMPORTANT STEROID ANALOGS

生物上重要的类固醇类似物的合成和纯化

• 批准号: 6240193
• 负责人: ROBERT M HOYTE
• 金额: $ 8.39万
• 依托单位: COLLEGE AT OLD WESTBURY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-01 至 1998-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6240193
• 关键词: androgen analog; androgen binding protein; androgen receptor; chemical structure function; chemical synthesis; glucocorticoids; high performance liquid chromatography; hormone binding protein; iodine; radionuclides; radiotracer; receptor binding; steroid analog; steroid hormone receptor

This project is concerned with the preparation of iodinated derivatives and analogs of steroid hormones in the androgen and glucocorticoid families. Synthetic procedures will be developed which will permit the incorporation of radioactive iodine (125I and 123I) into compounds which have either androgenic or glucocorticoid activity. Labeled androgens are expected to be useful for the sensitive detection of androgen responsive tumors such as prostate cancer and for quantifying the androgen receptor in vitro. The radioiodinated androgens will also have great utility for the autoradiographic studies of tissues, such as brain, in which the androgen receptor is present, but localized in specific cells or regions. Such studies have great potential value in elucidating the role of androgens in processes such as the sexual differentiation of the brain in fetal development. Labeled compounds with glucocorticoid activity will be valuable in mapping and imaging of glucocorticoid receptor rich regions of the brain also. Since the specific neurophysiological mechanisms by which corticosteroids influence neuronal function are not fully understood, such studies are of increasing importance in defining and understanding the role and function of these compounds in the brain. In this study the synthetic methodology will be worked out for the nonradioactive iodinated steroids, which will be purified and fully characterized using standard analytical techniques. The nonradioactive compounds will be tested for receptor binding in competition assays. Compounds found to be effective competitors will be prepared with the radioactive label and tested more fully for binding affinity (ka or Kd), specificity and binding to steroid plasma binding proteins. Eventually, their hormonal or antihormonal activity, receptor mediated distribution in vivo, nuclear translocation and metabolism will also be determined.

该项目涉及碘化衍生物的制备， 雄激素和糖皮质激素家族中的类固醇激素类似物。 将开发合成程序， 放射性碘（125 I和123 I）转化为化合物， 雄激素或糖皮质激素活性。 标记的雄激素预计将 可用于雄激素反应性肿瘤的灵敏检测， 前列腺癌和体外定量雄激素受体。 的 放射性碘标记的雄激素也将具有很大的效用， 组织的放射自显影研究，如脑，其中雄激素 受体存在，但定位于特定的细胞或区域。 等 研究在阐明雄激素在 胎儿大脑的性别分化等过程 发展 具有糖皮质激素活性的标记化合物将被 在糖皮质激素受体丰富区域的定位和成像中有价值， 大脑也是。 由于特定的神经生理机制， 皮质类固醇对神经元功能的影响尚未完全了解， 研究在定义和理解 以及这些化合物在大脑中的功能。 在这项研究中，将制定出合成方法， 非放射性碘化类固醇，这将是纯化和充分 使用标准分析技术表征。 非放射性 将在竞争测定中测试化合物的受体结合。 发现是有效竞争者的化合物将用以下物质制备： 放射性标记并更充分地测试结合亲和力（ka或Kd）， 特异性和结合类固醇血浆结合蛋白。 最后， 它们的激素或抗激素活性，受体介导的分布， 还将测定体内核易位和代谢。