CHOLECYSTOKININ ANTAGONIST

该项目的总体目标是扩展以前的研究， 通过合成一系列化合物， 基于早期研究中有希望的线索，并测试它们 在使用小细胞肺癌细胞的放射受体测定中的效力 （SCLC）和使用Fura-2- 负载（SCLC）细胞。 所提供的一般方法将最大限度地 拮抗剂肽的效力，然后在羧基- 已经显示出消除激动剂活性的末端（其中 预期受体结合将被维持）。 这一领域的以往工作主要遵循两种方法。 改性 已经测试了苯并二氮杂卓结构，并且 CCK-8已被修改。 各种衍生物表明， 受体类型，包括A型（胰腺或外周）、B型 （皮质或中央），和明显的C型（胃泌素）。 这项工作将 专注于开发B型或中枢CCK受体的拮抗剂。一 将合成一系列六种和七种氨基酸化合物。 两 环化肽也将被合成和研究。

The overall goal of this project is to extend previous studies on cholecystokinin (CCK) antagonists by synthesizing a series of compounds, based on promising leads from earlier studies, and to test them for potency in a radioreceptor assay using small cell lung carcinoma cells (SCLC) and in a bioassay for effects on cytosolic calcium using Fura-2- loaded (SCLC) cells. The general approach offered will maximize the potency of antagonist peptides and then make small changes at the carboxy- terminus that have been shown to eliminate agonist activity (with the expectation that receptor binding will be maintained). Previous work in this field has followed two main approaches. Modified benzodiazepine structures have been tested, and the peptide structure of CCK-8 has been modified. Various derivatives have indicated several receptor types, including type A (pancreatic or peripheral), type B (cortal or central), and apparently type C (gastrin). This work will focus on developing antagonists of type B or central CCK receptors. A series of six and seven amino acid compounds will be synthesized. Two cyclized peptides will also be synthesized and studied.