SYNTHESIS OF MODULATOR PHOSPHOLIPIDS

调节剂是糖皮质激素受体机制的细胞调节剂 可能还有其他类固醇受体机制。它的行动是 阻止受体复合体的激活和功能，并 稳定未激活形式的配体-受体相互作用。 其绝对结构的阐明及其衍生物的制备 可能是过度活跃的、拮抗剂或量身定做，以指定其对 特定的受体系统已变得极其重要。调制器具有 最近被提纯，其临时结构由 物理和化学方法得到一种乙醚-氨基磷脂。自.以来 调节剂的作用方式可能是解释激活的关键 受体复合体在细胞中的作用机制，关键是要有试剂 化合物的性质(具有明确的化学结构)到 发现它的作用机制。 制备调制器的新合成方法的发展 乙醚-磷脂是本课题的主要研究对象。我们会 设计即将开发的结构修饰的磷脂化合物 基于实验确定的调制要求 效力和特异度。合成将利用最近的技术 在首席调查员的实验室里开发出来的。合成材料 化合物将在首席合作调查员的实验室进行测试。 合成的化合物将用于确定化合物的绝对结构。 调节器；识别和评估每个结构组件的作用 在调节器的生物作用中；并设计和开发 激动剂和拮抗剂。放射性调制器将准备好 进行直接结合研究并开始描绘其细胞 退化。 除了深入了解大脑的正常生理功能 受体复合体，从程序中出现的结果可能会打开新的 制备作用于药物的化疗药物的可能性 受体，如乳腺癌中的抗雌激素受体和抗 前列腺癌中的雄激素受体。

Modulator is a cellular regulator of the glucocorticoid receptor mechanism and probably of other steroid receptor mechanisms. Its action is to prevent the activation and functioning of the receptor complex, and to stabilize the ligand-receptor interaction of the unactivated form. Elucidation of its absolute structure and preparation of derivatives which may be superactive, antagonists or tailor-made to specify its action on a specific receptor system has become extremely important. The modulator has been purified most recently, and its provisional structure determined by physical and chemical methods to be an ether-aminophospholipid. Since the mode of action of modulator may be the key to explaining the activation mechanism of the receptor-complex in the cell, it is vital to have reagent qualities of the compound (with well-defined chemical structure) to discover its mechanism of action. Development of new synthetic methods for the preparation of modulator ether-phospholipid is the main objective of this research project. We will design structurally modified phospholipid compounds that will be developed on the basis of experimentally determined requirements for modulating potency and specificity. The synthesis will utilize techniques recently developed in the principal investigator's laboratory. The synthetic compounds will be tested in the principal co-investigator's laboratory. The synthetic compounds will be used to determine the absolute structure of the modulator; to identify and assess the role of each structural component in the biological action of the modulator; and to design and develop agonists and antagonists. Radioactive modulator will be prepared to conduct direct binding studies and to begin to delineate its cellular degradation. In addition to gaining insight into the normal physiological functioning of the receptor-complexes, the results emerging from the program may open new possibilities for the preparation of chemotherapeutic agents acting at receptors, such as anti-estrogen receptors in breast cancer, and anti- androgen receptors in prostate cancer.