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The Combinatorial Design of Protein Molecular Switches

蛋白质分子开关的组合设计

基本信息

批准号：
7656069
负责人：
MARC A OSTERMEIER
金额：
$ 31.88万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-07-01 至 2012-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7656069
关键词：
Address Affinity Algorithms Ankyrin Repeat Arts Basic Science Behavior Binding Biochemical Biological Biological Assay Biosensor Bypass Cancer cell line Cell Line Cell physiology Cells Colon Colon Carcinoma Complex Coupling Cultured Cells Detection Development Diagnostic Engineering Enzymes Funding Gene Fusion Gene-Directed Enzyme Prodrug Therapy Genes Genetic Recombination Immunoassay In Vitro Lactamase Libraries Life Ligands MAPK8 gene MAPK9 gene Malignant Neoplasms Malignant neoplasm of prostate Mammalian Cell Methods Mitogen-Activated Protein Kinases Modality Molecular Mutation Normal Cell One-Step dentin bonding system Output PC3 cell line Peptides Phosphotransferases Prodrugs Protein Engineering Protein Kinase Proteins Reagent Reporter Research Proposals Screening procedure Signal Transduction Specificity Surface Switch Genes Testing Therapeutic Toxic effect Transplantation cancer cell cancer therapy combinatorial design enzyme activity expression vector genetic selection homologous recombination in vivo maltose-binding protein meetings member novel protein function public health relevance research study sensor theories therapeutic protein therapeutic target therapy design

项目摘要

DESCRIPTION (provided by applicant): Protein switches hold great promise as selective protein therapeutics and as biosensors for diagnostic and basic science applications; however, the creation of such proteins has proven difficult. We propose to create protein switches for these applications using a combinatorial method we developed that views all existing proteins as potential input and output modules for the desired switch. We will create a protein switch that will activate a prodrug only in cancer cells. Such a switch would have potential as a targeted therapeutic for the treatment of cancer. In addition, we will create switches to be used as sensors for kinases in vitro and in live cells. Switches to be used as sensors will be developed on a platform such that sensors for other proteins will be more readily created. Experiments proposed will also inform the study of how best to create switches. PUBLIC HEALTH RELEVANCE: Engineered protein switches hold great promise as selective protein therapeutics and as biosensors for diagnostic and basic science applications. We will develop switches designed for the treatment of cancer and switches designed to be used as sensors for the detection and quantification of important protein kinases in vitro and in live cells.

描述(申请人提供)：蛋白质开关作为选择性蛋白质疗法和诊断和基础科学应用的生物传感器具有很大的前景；然而，事实证明，创造这样的蛋白质是困难的。我们建议使用我们开发的组合方法来创建用于这些应用的蛋白质开关，该方法将所有现有的蛋白质视为所需开关的潜在输入和输出模块。我们将创造一个蛋白质开关，它只会激活癌细胞中的前药。这种转变有可能成为癌症治疗的靶向治疗方法。此外，我们将创造开关，用于在体外和活细胞中作为激酶的传感器。用作传感器的开关将在一个平台上开发，这样就可以更容易地创建其他蛋白质的传感器。建议的实验也将为研究如何最好地创造开关提供信息。与公共健康相关：工程蛋白质开关作为选择性蛋白质疗法以及诊断和基础科学应用的生物传感器前景广阔。我们将开发用于癌症治疗的开关，以及用于在体外和活细胞中检测和量化重要蛋白激酶的传感器的开关。