HIGH THROUGHPUT METHODS FOR G PROTEIN COUPLED RECEPTORS

G 蛋白偶联受体的高通量方法

• 批准号: 2865509
• 负责人: JESSE BAUMGOLD
• 金额: $ 10万
• 依托单位: RECEPTOR BIOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2865509
• 关键词: G protein; acidity /alkalinity; analytical method; drug discovery /isolation; fluorescence; fluorescent dye /probe; green fluorescent proteins; method development; receptor coupling

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

描述：（改编自申请人的摘要） 项目将开发新的和改进的方法，以高效 G蛋白耦合受体的吞吐量筛选以发现药物 目的。 G蛋白偶联受体包括大型细胞的超家族 表面蛋白是许多已知药物的靶标。其中包括 一类受体是孤儿受体，其天然配体未知。 目前，这些受体很难筛选。提出的方法 筛选已知和孤儿G蛋白的更容易 耦合受体。我们提出耦合绿色的pH敏感衍生物 荧光蛋白到几个G蛋白的氨基末端 受体。激活后，这些受体将内部化到 大概pH值较低的内吞膜。如果是这样，我们希望看到 荧光特征的变化。如果有效，我们建议 将这项技术扩展到许多已知和孤儿的受体，最终 将这些测定的商业化到药物发现市场。 拟议的商业应用程序：不可用