High Throughput, Label-Fee Molecular Interaction Platform for Membrane Protein Ta

描述（由申请人提供）：分子相互作用是健康代谢的基础，也是疾病的表现，是药物治疗的基础。可用于研究分子在初始环境和生理浓度下相互作用的工具，如表面固定化或标记，是有限的。目前的无标签技术不能进行膜蛋白靶相互作用的均匀（自由溶液）测量。膜蛋白约占人类蛋白质组的1/3，与广泛的生物相关物种相互作用。被称为g蛋白偶联受体（GPCR）的一类特殊膜蛋白引起了特别的兴趣，因为它们代表了大约40%的处方药和超过一半的前100名最畅销药物的主要药物靶点。目前，还没有一种实用的无标记的方法来研究GPCR -铅在其原生环境中的相互作用。因此，无标记方法明显不能满足主要药物发现的需求，因此，存在对无标记技术的深刻需求，以支持所有重要的GPCR和膜蛋白领域的研究需求。分子传感公司（MSI）的二期SBIR提案题为“膜蛋白靶点的高通量、无标签分子相互作用平台”，利用我们一期项目的成果，旨在生产一种用于药物研究的强大的后向散射干涉测量（BSI）仪器。除了完善平台之外，在第二阶段，我们将展示BSI的独特优势和能力，通过与三个世界级研究环境的合作，在膜蛋白药物研究的所有重要领域取得重大进展：加州大学伯克利分校的格罗夫斯实验室，斯克里普斯研究所的芬恩实验室和范德比尔特大学的伯恩霍普实验室。我们的第二阶段项目的高潮将导致原型研究产品的创建，该公司将出售给其在转化和制药研究市场的早期客户。第三阶段活动将完成产品开发过程，使世界各地的实验室都能使用这种强大的新工具。正如我们第一阶段技术的初始市场经验所告诉我们的那样，我们的商业产品将对基础、转化和药物发现研究产生持续的影响，通过加速释放和开发新的强大的治疗和诊断方法，积极影响医疗保健，这与美国国立卫生研究院的使命是一致的。

DESCRIPTION (provided by applicant): Molecular interactions form the basis of healthy metabolism as well as the manifestation of disease, and comprise the very foundation of drug treatment. Tools available to study molecular interactions in their nascent environment and physiological concentrations without chemical modification, such as surface immobilization or labeling, are limited. Current label-free technologies cannot perform homogeneous (free solution) measurements of membrane protein target interactions. Membrane proteins, which make up about 1/3 of the human proteome, interact with a wide range of biologically relevant species. A specific class of membrane proteins known as G-protein coupled receptors (GPCR) is of particular interest, as they represent the principle drug target for about 40% of all prescription pharmaceuticals and over half of the top one hundred best selling drugs. Currently, there does not exist a practical label-free means to study GPCR - lead interactions as they proceed in their native environment. Consequently, label-free approaches significantly under-serve a major drug discovery need, and as such, there exists a profound requirement for a label-free technique to support research demands in the all important GPCR and membrane protein fields. Molecular Sensing Inc.'s (MSI) Phase II SBIR proposal entitled, "High Throughput, Label-free Molecular Interaction Platform for Membrane Protein Targets," leverages the achievements of our Phase I program and is directed towards producing a robust Back-Scattering Interferometry (BSI) instrument for use in drug research. In addition to refining the platform, under Phase II we will demonstrate the unique strengths and capabilities of BSI to significantly advance progress in the all important area of membrane protein drug research by capitalizing on collaborations with three world-class research environments: The Groves Laboratory at the University of California at Berkeley, the Finn Laboratory of Scripps Research Institute, and the Bornhop Laboratory at Vanderbilt University. The culmination of our Phase II program will result in the creation of a prototype research product, which the company will sell to its early access customers in translational and pharmaceutical research markets. Phase III activities will complete the product development process, making this powerful new tool accessible to laboratories worldwide. As our initial market experience of Phase I technology has taught, our commercial product will create a sustained impact to basic, translational, and drug discovery research that will positively influence healthcare through the accelerated release and development of new and powerful therapeutics and diagnostics, consistent with the mission of the National Institutes of Health. PUBLIC HEALTH RELEVANCE: High Throughput, Label-Fee Molecular Interaction Platform for Membrane Protein Targets Drugs directed against cell membrane targets comprise one of the most important classes of therapeutics and focused pharmaceutical research. Tools available to support this research lack enabling capabilities, and are a barrier to progress. Our program will result in the creation of a novel research platform that will exert a substantial and powerful impact to advance progress in membrane target drug research, yielding new and improved therapeutics that will positively impact the treatment of disease, improving healthcare while reducing its cost.