QCM Quantification of Endocrine Disruptor Activity

内分泌干​​扰物活性的 QCM 定量

• 批准号: 6882801
• 负责人: XIANGQUN ZENG
• 金额: $ 8.54万
• 依托单位: OXFORD BIOMEDICAL RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2006-03-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6882801
• 关键词: DNA binding protein; animal genetic material tag; animal tissue; biochemistry; biomedical equipment development; biosensor device; electrochemistry; endocrine disorder; estrogen receptors; fluorescence; gene environment interaction; gene expression; genetic regulatory element; genetic transcription; high throughput technology; intermolecular interaction; macromolecule; nucleic acid sequence; receptor binding; surface plasmon resonance

DESCRIPTION (provided by applicant): Environmental agents with estrogen-like activity are a major public health issue. Although a variety of assays have been developed to detect binding to the estrogen receptor (ER) and other assays have been developed to monitor subsequent effects on estrogen sensitive gene transcription, an Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) recently reported difficulties with all available methods. We are developing quartz crystal microbalance (QCM) platform technology for the quantitative high-throughput analysis of complex macromolecular interactions. The focus of this project is the development of QCM biosensors for rapid quantification of the influence of endocrine disrupters on the interactions among the estrogen receptor (ER), coactivators or corepressors and the estrogen response element (ERE). QCM has been applied to study interactions of proteins with small molecules, protein-protein interactions, and DMA hybridization. It is expected that QCM will provide heretofore inaccessible quantitative information regarding effects of endocrine disrupters on the kinetics and affinity of the ER for the ERE as well as comparable information about the influence of endocrine disrupters on interactions between the ER and coactivators, corepressors, and other transcription factors whose interactions regulate estrogen-responsive genes in many cell types and organisms. Major advantages of QCM include high sensitivity, low cost, real time label-free, quantitative analysis. Given the U.S. congressional mandate and World Health Organization recommendations for endocrine disrupter testing of chemicals, we anticipate strong market demand for ERE biosensor technology.

描述（由申请人提供）：具有类雌激素活性的环境因子是一个主要的公共卫生问题。尽管已经开发出多种检测方法来检测与雌激素受体 (ER) 的结合，并且还开发了其他检测方法来监测对雌激素敏感基因转录的后续影响，但替代方法验证机构间协调委员会 (ICCVAM) 最近报告了困难与所有可用的方法。 我们正在开发石英晶体微天平（QCM）平台技术，用于复杂大分子相互作用的定量高通量分析。该项目的重点是开发 QCM 生物传感器，用于快速量化内分泌干扰物对雌激素受体 (ER)、共激活剂或辅阻遏物以及雌激素反应元件 (ERE) 之间相互作用的影响。 QCM 已应用于研究蛋白质与小分子的相互作用、蛋白质-蛋白质相互作用和 DMA 杂交。预计 QCM 将提供迄今为止无法获得的关于内分泌干扰物对 ER 动力学和 ERE 亲和力影响的定量信息，以及关于内分泌干扰物对 ER 与共激活剂、辅阻遏物和其他物质之间相互作用的影响的类似信息。转录因子，其相互作用调节许多细胞类型和生物体中的雌激素反应基因。 QCM的主要优点包括高灵敏度、低成本、实时免标记定量分析。鉴于美国国会对化学品内分泌干扰物测试的授权和世界卫生组织的建议，我们预计市场对 ERE 生物传感器技术的需求强劲。