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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，无论是直接还是间接的，都是针对膜蛋白的。膜蛋白阵列将成为药物筛选和学术研究实验室研究蛋白质与脂质、蛋白质与膜蛋白相互作用以及治疗药物的重要工具。虽然其他微阵列技术如DNA和抗体微阵列已经发展得很好，但膜蛋白微阵列还不能满足生物医学研究和药物筛选的需要。生命生物科学公司(LBSI)计划开发一种商业上可行的膜蛋白阵列系统，通过克服现有的技术障碍，能够以高复用和高通量的方式研究膜蛋白功能和相互作用。第一阶段的研究将集中于开发微阵列平台，并验证该平台对生产功能性膜蛋白阵列的普遍适用性。在第二阶段，我们将把系统扩展到更多的G蛋白偶联受体(GPCRs)微阵列，并整合一个高灵敏度的检测系统，以构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。该平台将大大加快蛋白质-脂质、蛋白质-膜蛋白、药物-膜蛋白以及药物-膜相互作用的研究，并将有助于开发和筛选针对多种疾病状态的药物，包括癌症、炎症性疾病、传染病、心脏病和肾脏疾病。与公共卫生相关：生物膜蛋白在所有生命系统中都发挥着重要作用。发展膜蛋白阵列的拟议研究满足了膜蛋白功能和药物筛选和表征领域的重要需求。膜蛋白阵列将用于开发有效和安全的治疗药物，用于治疗多种疾病，如癌症、糖尿病、炎症和心脏功能障碍。