HIGH THROUGHPUT SCREENING ASSAY DEVELOPMENT FOR PHARMACOPERONES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 其具体目的是生产和验证用于从分子库中识别药物的筛选，这些筛选通过一种新的治疗方法发挥其作用，控制翻译后蛋白质折叠，从而控制细胞运输和挽救突变蛋白质。G蛋白偶联受体(GPCRs)经常是文库筛选的目标，然而这种方法通常依赖于识别激动剂或拮抗剂的筛查，并且可能会错过许多将在建议的筛查中确定的药物。我们的方法在治疗方法上识别出具有相当大程度的新颖性的药物，依赖于目前在分子库分析管道中没有表现出来的细胞机制；这为HTS方法的使用提供了一个尚未开发的机会。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The specific aim is to produce and validate screens for identification of pharmacoperone drugs from molecular libraries which exert their actions by a newly appreciated therapeutic approachnamely, control of post-translational protein folding and, as a consequence, cellular trafficking and rescue of mutated proteins. G protein coupled receptors (GPCRs) are frequently targeted in library screening, yet this approach generally relies on screens that identify agonists or antagonists and would have missed many of the drugs that will be identified in the proposed screens. Our approach identifies drugs with a significant degree of novelty in therapeutic approach, relying on cellular mechanisms that are not currently represented in the Molecular Libraries assay pipeline; this offers an untapped opportunity for use of the HTS approach.