Inhibitor mediated protein degradation

抑制剂介导的蛋白质降解

• 批准号: 8607196
• 负责人: Lizbeth K. Hedstrom
• 金额: $ 30.74万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8607196
• 关键词: Affinity; Affinity Chromatography; Animal Model; Arginine; Basic Science; Biocompatible; Biological; Biological Assay; Biological Process; Carbamates; Cells; Chimeric Proteins; DHFR gene; DNA Repair Enzymes; Dasatinib; Dihydrofolate Reductase; Dissociation; Elements; Escherichia coli; Ethacrynic Acid; Glutathione S-Transferase; Hereditary Disease; Investigation; Ligands; Link; Mediating; Methods; NMR Spectroscopy; Organism; Pathway interactions; Pharmacologic Substance; Phosphotransferases; Post-Translational Regulation; Proteins; S-nitro-N-acetylpenicillamine; Structure-Activity Relationship; System; Technology; Translational Research; Trimethoprim; Work; cancer therapy; chemotherapy; drug discovery; effective therapy; inhibitor/antagonist; multicatalytic endopeptidase complex; novel; novel strategies; protein degradation; protein expression; protein function; research study; small molecule; tool

DESCRIPTION (provided by applicant): A formidable toolkit exists for manipulating protein expression at the transcriptional level, but the methods for the post-translational modulation of proteins are few and of limited utility. A small molecule that induces degradation of endogenous proteins would clearly be a tremendously useful tool for probing protein function and an exciting approach for chemotherapy. The challenge is to develop technology that is biocompatible and widely applicable. We have serendipitously discovered a moiety that when combined with a recognition element, induces degradation of the target protein. We propose to characterize this phenomenon and develop these novel tools for protein knockdown that will be invaluable in a broad array of biological and pharmaceutical applications.

描述（由申请人提供）：存在用于在转录水平操纵蛋白质表达的强大工具包，但用于蛋白质翻译后调节的方法很少且实用性有限。诱导内源性蛋白质降解的小分子显然将是探测蛋白质功能的非常有用的工具，也是令人兴奋的化疗方法。挑战在于开发生物相容且广泛适用的技术。我们偶然发现了一个部分，当与识别元件结合时，会诱导目标蛋白的降解。我们建议描述这种现象，并开发这些用于蛋白质敲低的新工具，这在广泛的生物和制药应用中将具有无价的价值。