Obliquely deposited substrates for detection of Ras

关键的细胞信号分子，如Ras，在癌变过程中起着核心作用，并且是新一代抑制蛋白激酶药物的靶标。沿着整个途径测量分子激活状态的能力变得越来越重要，然而现有的技术不足以满足对简单分析的需求，这些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检测的需求。鸭嘴兽技术是一种新颖的、广泛应用的平台纳米技术，它基于液晶对表面纳米尺度特征的敏感性。该技术允许高度敏感的分子相互作用检测，并适用于自动化和多路复用格式。在本课题中，我们将利用具有各向异性形貌的金膜，优化总Ras和活化Ras的检测和定量技术。建议的商业应用：鸭嘴兽技术是一项具有广泛应用潜力的革命性平台技术。一种快速分析总Ras和活化Ras的方法将有很大的市场，并形成一种设备的基础，用于测量沿着信号通路的多个分子，确定它们的数量和相对的激活部分。

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.