SIGNAL TRANSDUCTION BIOSENSORS FOR ANTI-CANCER HTS

用于抗癌 HTS 的信号传导生物传感器

• 批准号: 6293878
• 负责人: ROBERT F BALINT
• 金额: $ 10万
• 依托单位: PANORAMA RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6293878
• 关键词: antineoplastics; beta lactamase; biological signal transduction; biosensor device; growth factor receptors; high throughput technology; intermolecular interaction; molecular cloning; neoplastic cell; oncogenes; phosphorylation; protein protein interaction; technology /technique development; tissue /cell culture

DESCRIPTION (applicant's abstract): The Achilles heel of most current high-throughput screening (HTS) strategies is the inherent inefficiencies of the available screening assay platforms, leading to excessive rates of false positive and false negative selection. To address the need for more efficient screening assay platforms, we have developed a series of universal biosensors-based on engineered beta-lactamases which can be adapted for activation or inactivation by virtually any protein-protein or protein-ligand interaction that occurs naturally in cells, including those that are modulated by post-translational modifications such as phosphorylation. Thus for rapid and efficient selection of inhibitors of any interaction of interest from large natural or synthetic compound libraries, our engineered beta-lactamases may be set up to be quantitatively inhibited by the target interaction, so that a robust positive signal is produced in the presence of even modest amounts of an inhibitor. In Phase I we will develop a beta-lactamase biosensor for positive signal detection in tumor cells of inhibitors of the phosphorylation-dependent interaction between the signaling protein Grb2 and the oncogenic growth factor receptor ErbB2. In Phase II we will use this biosensor to screen the NCI natural products library, and we will develop additional biosensors. PROPOSED COMMERCIAL APPLICATION: The primary goal of this work is to accelerate the drug discovery process for cancer chemotherapy.

描述（申请人摘要）：大多数当前的致命弱点