Obliquely deposited substrates for detection of Ras

关键的细胞信号分子，如RAS，在致癌过程中发挥着核心作用，是新一代抑制蛋白激酶药物的靶点。测量整个途径上分子的激活状态的能力越来越重要，但现有的技术不足以满足对简单分析的需求，这些简单的分析允许同时测试几个分子，并可以确定它们的总浓度、激活状态和翻译后修饰，如磷酸化或法尼化。蛋白激酶抑制剂和相关化合物进入临床试验将增加学术、制药和临床实验室对此类分析的需求。鸭嘴兽技术是一种新型的、应用广泛的平台型纳米技术，其基础是液晶对表面纳米尺度特征的敏感性。该技术允许对分子相互作用进行高度灵敏的检测，并适用于自动化和多路复用格式。在这项建议中，我们将优化总RAS和活化RAS的检测和定量技术，利用具有各向异性形貌的金膜。商业应用建议：鸭嘴兽技术是一项革命性的平台技术，具有广阔的应用潜力。一种快速分析总RAS和激活RAS的方法将有很大的市场，并为测量沿信号通路的多个分子，确定它们的数量和激活的相对部分奠定基础。

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.