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 阻止受体复合物的激活和功能，以及 稳定未活化形式的配体-受体相互作用。 其绝对结构的解析和衍生物的制备， 可以是超活性的，拮抗剂或定制的，以指定其对 特异性受体系统变得极其重要。 调制器具有 最近被纯化，其临时结构由 采用物理和化学方法制备醚氨基磷脂。 以来 调节剂的作用方式可能是解释激活的关键 在细胞中的受体复合物的机制，它是至关重要的试剂 化合物的性质（具有明确的化学结构）， 发现其作用机制。 调节剂合成新方法的研究进展 醚磷脂是本研究项目的主要目标。 我们将 设计结构修饰的磷脂化合物， 基于实验确定的调制要求 效力和特异性。 合成将利用最近的技术 是在首席研究员的实验室里研发的 合成 化合物将在主要合作研究者的实验室进行测试。 合成的化合物将用于确定的绝对结构 调节剂;识别和评估每个结构组分的作用 调节剂的生物作用;并设计和开发 激动剂和拮抗剂。 将制备放射性调节剂， 进行直接结合研究，并开始描绘其细胞 降解 除了深入了解正常的生理功能， 受体复合物，从程序中出现的结果可能会打开新的 制备作用于 受体，如乳腺癌中的抗雌激素受体，以及抗 雄激素受体在前列腺癌中的作用

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.