Developing functional membrane protein arrays for highly efficient drug screening

开发功能性膜蛋白阵列以实现高效药物筛选

基本信息

批准号：
8200663
负责人：
XICHUN ZHOU
金额：
$ 15万
依托单位：
3D GLASS SOLUTIONS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-15 至 2013-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8200663
关键词：
Address Antibodies Area Biochemical Biological Biological Assay Biomedical Research Cardiac Cell membrane Cell physiology Cells Communicable Diseases DNA Dehydration Detection Development Diabetes Mellitus Disease Drug Delivery Systems Environment Feasibility Studies Film Fluorescence Resonance Energy Transfer Functional disorder Future G-Protein-Coupled Receptors Glass Heart Diseases Immobilization Inflammation Inflammatory Investigation Kidney Diseases Laboratory Research Laboratory Study Lead Life Ligand Binding Lipid Bilayers Lipids Malignant Neoplasms Marketing Measures Membrane Membrane Lipids Membrane Proteins Methods Microarray Analysis Modeling Organism Pattern Peptides Pharmaceutical Preparations Phase Play Preclinical Drug Evaluation Printing Protein Array Protein Binding Protein Microchips Proteins Reporting Research Robotics Role Screening procedure Signal Pathway Spottings System Therapeutic Therapeutic Agents Variant Vesicle base drug development drug discovery interest phase 1 study protein function research and development small molecule success therapeutic target tool

项目摘要

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.

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。绝大多数的小分子药物直接或间接靶向膜蛋白。在蛋白质与脂质，蛋白质和膜蛋白以及治疗药物之间相互作用的研究中，膜蛋白的阵列将是药物筛查和学术研究实验室的重要工具。尽管其他微阵列技术（例如DNA和抗体微阵列）已经发达了，但膜蛋白微阵列已经发达，以满足生物医学研究和药物筛查的需求。 Life Bioscience Inc.（LBSI）建议开发一种能够通过克服当前技术障碍来研究膜蛋白功能和相互作用的商业上可行的膜蛋白阵列系统。第一阶段的研究将着重于开发微阵列平台，并验证平台生产功能性膜蛋白阵列的一般适用性。在第二阶段，我们将将系统扩展到更高的多重G蛋白偶联受体（GPCRS）微阵列，并结合了高灵敏度检测系统，以组成用于蛋白质功能分析和药物筛查应用的完整膜蛋白测定平台。该平台将大大加速蛋白质脂质，蛋白质 - 膜蛋白，药物 - 膜蛋白和药物 - 膜相互作用的研究，并将有助于针对多种疾病状态的药物的开发和筛查，包括癌症，炎性疾病，感染性疾病，心脏病，心脏病，心脏病和肾脏疾病。公共卫生相关性：生物膜蛋白在所有生物系统中都起着重要作用。拟议的开发膜蛋白阵列的研究解决了膜蛋白功能以及药物筛查和表征的重要需求。膜蛋白阵列将有助于开发有效且安全的治疗剂，以治疗癌症，糖尿病，炎症和心脏功能障碍等广泛疾病。