HIGH THROUGHPUT METHODS FOR G PROTEIN COUPLED RECEPTORS

描述：(改编自申请者摘要)这项计划的总体目标 项目是开发新的和改进的方法，用来执行高 药物开发中G蛋白偶联受体的通过量筛选 目的。G蛋白偶联受体包括一个大的细胞超家族 表面蛋白是许多已知药物的靶标。包括在此 这类受体是天然配体未知的孤儿受体。 目前，这些受体很难筛选。建议的方法 将使筛查已知和孤立的G蛋白变得容易得多 偶联受体。我们建议将Green的一个pH敏感的衍生物偶联 几种偶联G蛋白氨基末端的荧光蛋白 感受器。一旦激活，这些受体就会内化到 可能具有较低pH值的内吞细胞膜。如果是这样，我们预计会看到 荧光特性的变化。如果这起作用，我们建议 将这项技术扩展到许多已知的和孤立的受体，并最终 将这些分析商业化，推向药物发现市场。 建议的商业应用：不可用

DESCRIPTION: (adapted from applicant's abstract) The overall goal of this project is to develop new and improved methodology with which to perform high throughput screening of G protein coupled receptors for drug discovery purposes. G protein coupled receptors include a large superfamily of cell surface proteins that are targets for many of the known drugs. Included in this class of receptors are orphan receptors whose natural ligands are unknown. Currently these receptors are difficult to screen. The proposed methodology will make it considerably easier to screen both known and orphan G protein coupled receptors. We propose coupling a pH-sensitive derivative of Green Fluorescent Protein to the amino terminus of several G protein coupled receptors. Upon activation, these receptors undergo internalization to endocytic membranes that presumably have a lower pH. If so, we expect to see changes in the fluorescence characteristics. If this works, we propose expanding this technology to many known and orphan receptors and eventually commercializing these assays to the drug discovery market. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE