Biosensor Studies of Estrogenic Compounds with hER-A & B

hER-A 雌激素化合物的生物传感器研究

• 批准号: 6405898
• 负责人: Judith L. Erb
• 金额: $ 40.03万
• 依托单位: IA, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2003-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6405898
• 关键词: bioengineering /biomedical engineering; biomedical equipment development; biosensor device; biotechnology; diethylhexylphthalate; drug screening /evaluation; environmental exposure; estrogen analog; estrogen receptors; fiber optics; fluorescent dye /probe; gel mobility shift assay; genistein; intermolecular interaction; phytoestrogens; protein isoforms; receptor binding

DESCRIPTION (provided by applicant): During Phase I, IA Inc. and HRL developed a novel, regenerable, fiber optic biosensor for monitoring in real-time, molecular interactions between estrogen receptor modulators and both hER-alpha and hER-beta. These biosensors don't require fluorophore labeling of receptor, are more specific than sensors monitoring mass on the sensor surface, and utilize only 10 femtomoles of receptor per sample. Sensors provide a kinetic association and dissociation curve for a compound in 9-10 minutes. Sensor data on the interaction between a variety of xeno-, phyto- and endogenous estrogens and hER-alpha or hER-beta generally agrees with previously reported binding studies. Exciting new data was also obtained. Of particular significance is the observation that genistein, a phytoestrogen believed to be protective against certain cancers, produces a greater increase in stable complex formation between ERE and hER-beta than it does with hER-alpha. Also diethyl phthalate, a compound widely used in colognes and cosmetics, selectively activates formation of stable complex between ERE and hER-alpha but not hER-beta. Phase II work will develop a prototype instrument and further explore the possibility of distinguishing between beneficial and harmful estrogen receptor modulators by kinetic measurements using hER-alpha and hER-beta. PROPOSED COMMERCIAL APPLICATION: Not Available

描述（由申请人提供）：在第I阶段，IA Inc. HRL开发 一种新型的、可再生的、用于实时监测的光纤生物传感器， 雌激素受体调节剂和hER-α之间的分子相互作用 和hER-β。这些生物传感器不需要受体的荧光团标记， 比监测传感器表面质量的传感器更具体， 每个样品仅利用10飞摩尔的受体。传感器提供了一种动力学 在9-10分钟内化合物的缔合和解离曲线。传感器数据 各种外源性、植物性和内源性雌激素之间的相互作用 hER-α或hER-β通常与先前报道的结合一致 问题研究还获得了令人振奋的新数据。特别重要的是 观察到染料木黄酮，一种植物雌激素，被认为是保护， 在某些癌症中， 而不是hER-α。邻苯二甲酸二乙酯， 化合物广泛用于古龙水和化妆品，选择性激活形成 ERE和hER-α而不是hER-β之间的稳定复合物。二期工程 将开发一个原型仪器，并进一步探讨 区分有益和有害的雌激素受体调节剂， 使用hER-α和hER-β进行动力学测量。 拟定商业应用： 不可用