Developing functional membrane protein arrays for highly efficient drug screening

描述（由申请人提供）：膜蛋白是细胞间信号通路的重要组成部分。绝大多数小分子药物直接或间接地以膜蛋白为靶点。膜蛋白阵列将成为药物筛选和研究蛋白质与脂质、蛋白质与膜蛋白以及治疗药物相互作用的学术研究实验室的重要工具。虽然其他的微阵列技术如DNA和抗体微阵列已经发展得很好，但膜蛋白微阵列技术在生物医学研究和药物筛选方面还不够成熟。Life BioScience Inc. （LBSI）提出开发一种具有商业可行性的膜蛋白阵列系统，该系统能够以高复用和高通量的方式研究膜蛋白的功能和相互作用。第一阶段的研究将侧重于开发微阵列平台，并验证该平台在生产功能性膜蛋白阵列方面的一般适用性。在第二阶段，我们将扩展系统到更高的多重g蛋白偶联受体（gpcr）微阵列，并结合一个高灵敏度检测系统，以组成一个完整的膜蛋白分析平台，用于蛋白质功能分析和药物筛选应用。该平台将极大地加速蛋白质-脂质、蛋白质-膜蛋白、药物-膜蛋白和药物-膜相互作用的研究，并将有助于开发和筛选针对各种疾病状态的药物，包括癌症、炎症性疾病、传染病、心脏病和肾脏疾病。

DESCRIPTION (provided by applicant): Membrane proteins are an essential component of intercellular signaling pathways. The overwhelming majority of small molecule drugs, either directly or indirectly, target membrane proteins. Arrays of membrane proteins would be important tools in drug screening and academic research laboratories in studies of interactions between proteins and lipids, proteins and membrane proteins, as well as therapeutic drugs. Although other microarrays technologies such as DNA and antibody microarrays have been well- developed, membrane protein microarray has been under-developed to fulfill the needs in biomedical research and drug screening. Life BioScience Inc. (LBSI) proposes to develop a commercially viable membrane protein array system capable of studying membrane protein function and interactions in a high multiplexed and high throughput manner by overcoming current technical barriers. Phase I studies will focus on developing microarray platform and validating the general applicability of the platform to produce functional membrane protein arrays. In Phase II we will expand the system to higher multiplex G-protein-coupled receptors (GPCRs) microarrays and incorporate a high sensitivity detection system to comprise a complete membrane protein assay platform for protein functional analysis and drug screening applications. This platform will drastically accelerate investigations of protein-lipid, protein-membrane protein, drug-membrane protein, and drug-membrane interactions, and will be useful in the development and screening of drugs targeting a variety of disease states, including cancer, inflammatory diseases, infectious diseases, heart disease, and kidney disease. PUBLIC HEALTH RELEVANCE: Biological membrane proteins play an important role in all living systems. The proposed research in developing membrane protein arrays addresses important needs in the areas of membrane protein function and drug screening and characterization. The membrane protein arrays will be useful in the development of effective and safe therapeutic agents for the treatment of wide range diseases such as cancer, diabetes, inflammation, and cardiac dysfunction.