Obliquely deposited substrates for detection of Ras

用于 Ras 检测的倾斜沉积底物

• 批准号: 6480203
• 负责人: Barbara A. Israel
• 金额: $ 14.92万
• 依托单位: PLATYPUS TECHNOLOGIES, LLC
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-22 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6480203
• 关键词: antigen antibody reaction; biological signal transduction; enzyme activity; enzyme inhibitors; enzyme substrate; gold; guanine nucleotide binding protein; intermolecular interaction; liquid crystal; nanotechnology; nucleic acid amplification techniques; nucleic acid quantitation /detection; posttranslational modifications; technology /technique development

Key cell signaling molecules, such as Ras, play a central role in carcinogenesis and are the targets for a new generation of drugs that inhibit protein kinases. The ability to measure the activation status of molecules along an entire pathway is of increasing importance, yet the available technologies are inadequate to handle the demand for simple assays that permit simultaneous testing of several molecules and can determine their total concentration, activation status, and post- translational modifications, such as phosphorylation or farnesylation. The movement of protein kinase inhibitors and related compounds into clinical trials will increase the demand for such assays in academic, pharmaceutical and clinical laboratories. Platypus technology is a novel, broadly applicable platform nanotechnology based on the sensitivity of liquid crystals to nanoscale features in surfaces. The technology permits highly sensitive detection of molecular interactions and is adaptable to automated and multiplexed formats. In this proposal, we will optimize the technology for the detection and quantification of total Ras and activated Ras, utilizing gold films with anisotropic topography. PROPOSED COMMERCIAL APPLICATIONS: Platypus Technology is a revolutionary platform technology with broad application potential. A rapid method for the analysis of total and activated Ras will have a large market and form the basis of a device to measure multiple molecules along a signaling pathway, determine their amounts and the relative portion of activation.

关键细胞信号分子（例如RAS）在癌变中起着核心作用，并且是抑制蛋白激酶的新一代药物的靶标。 测量沿整个途径的分子激活状态的能力具有越来越重要的重要性，但是可用的技术不足以处理对几个分子同时测试的简单测定需求，并且可以确定它们的总浓度，激活状态和后翻译后的修饰，例如磷酸化或phosphorathation或Farseation praphosphoration或Farnesyletation。蛋白激酶抑制剂和相关化合物向临床试验的运动将增加对学术，药物和临床实验室中这种测定的需求。 鸭嘴兽技术是一种基于液晶对表面中纳米级特征的敏感性的新颖，广泛的平台纳米技术。 该技术允许对分子相互作用的高度敏感检测，并适应自动化和多重格式。 在此提案中，我们将优化用于检测和定量总RA和激活RA的技术，利用具有各向异性地形的黄金膜。拟议的商业应用：鸭嘴兽技术是具有广泛应用潜力的革命性平台技术。 用于分析总RA的快速方法将具有较大的市场，并构成了沿信号通路，确定其量和激活的相对部分测量多个分子的设备的基础。