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

高通量、免标记的膜蛋白 Ta 分子相互作用平台

• 批准号: 8201152
• 负责人: Scot Randy Weinberger
• 金额: $ 126.06万
• 依托单位: MOLECULAR SENSING, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-26 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8201152
• 关键词: Achievement; Acinetobacter baumannii; Address; Antibiotic Resistance; Applied Research; Area; Back; Binding; Binding Proteins; Biological Assay; Biological Models; Bradykinin; California; Categories; Cell membrane; Chemicals; Chemistry; Collaborations; Computer software; Custom; Data Analyses; Development; Devices; Diagnostic; Diffusion; Disease; Drug Delivery Systems; Educational process of instructing; Environment; Failure; Fees; Fluorescein-5-isothiocyanate; Fluorescence; Foundations; G-Protein-Coupled Receptors; Healthcare; Hour; Human; Immobilization; Interferometry; Isoenzymes; Label; Laboratories; Lead; Letters; Libraries; Ligands; Lipids; Market Research; Marketing; Measurement; Measures; Membrane; Membrane Proteins; Metabolism; Microfluidics; Microscopic; Mission; Modification; Molecular; Noise; Optics; PH Domain; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phosphatidylinositols; Phospholipase D; Physiological; Preparation; Process; Protein Binding; Proteins; Proteome; Recovery; Research; Research Design; Research Institute; Research Support; Robotics; Sampling; Screening procedure; Series; Signal Transduction; Site; Small Business Innovation Research Grant; Solutions; Specificity; Surface; System; Systems Analysis; Techniques; Technology; Testing; Texas red; Therapeutic; Time; Training; United States National Institutes of Health; Universities; base; cost; drug discovery; experience; improved; inhibitor/antagonist; instrument; interest; meetings; novel; operation; pathogenic bacteria; platelet protein P47; product development; programs; prototype; receptor; research and development; research study; therapeutic target; tool

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.

描述（由申请人提供）：分子相互作用形成健康代谢的基础以及疾病的表现，并构成药物治疗的基础。可用于研究分子在其新生环境和生理浓度下的相互作用而无需化学修饰（如表面固定或标记）的工具有限。目前的无标记技术不能进行膜蛋白靶相互作用的均相（游离溶液）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）的一类特定的膜蛋白特别令人感兴趣，因为它们代表了约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标。目前，不存在一种实用的无标记方法来研究GPCR -铅相互作用，因为它们在其天然环境中进行。因此，无标记方法显著地不足以满足主要药物发现需求，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。分子传感公司的（MSI）第二阶段SBIR提案，题为“膜蛋白靶点的高通量、无标记分子相互作用平台”，利用了我们第一阶段计划的成就，旨在生产一种强大的背散射干涉测量（BSI）仪器用于药物研究。除了完善平台，在第二阶段，我们将展示BSI的独特优势和能力，通过利用与三个世界级研究环境的合作，显着推进膜蛋白药物研究的所有重要领域的进展：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兰实验室和范德比尔特大学的伯恩霍普实验室。我们的第二阶段计划的高潮将导致创建一个原型研究产品，该公司将出售给其抢先体验客户在转化和制药研究市场。第三阶段的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一强大的新工具。正如我们第一阶段技术的初步市场经验所教导的那样，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，这将通过加速发布和开发新的强大的治疗和诊断方法对医疗保健产生积极影响，这与美国国立卫生研究院的使命一致。 公共卫生关系：针对细胞膜靶点的药物是最重要的一类治疗药物，也是药物研究的重点。可用于支持这项研究的工具缺乏使能能力，是取得进展的障碍。我们的计划将导致创建一个新的研究平台，这将对推进膜靶向药物研究的进展产生重大而强大的影响，产生新的和改进的治疗方法，这将对疾病的治疗产生积极影响，改善医疗保健，同时降低其成本。