Biosensor for Screening specific Interactions with AhR

用于筛选与 AhR 特异性相互作用的生物传感器

• 批准号: 6443692
• 负责人: Judith L. Erb
• 金额: $ 9.99万
• 依托单位: IA, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2002-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6443692
• 关键词: aromatic hydrocarbon receptor; bioengineering /biomedical engineering; biosensor device; chemical kinetics; endocrinology; estrogen receptors; fiber optics; hormone analog; hormone inhibitor; intermolecular interaction; molecular chaperones; technology /technique development

Understanding the mechanisms by which chemical compounds and drugs interact with both the aryl hydrocarbon receptor (AhR) and estrogen receptor (ER) signaling pathways is important both for identifying potential environmental and endocrine disruptors and for screening compounds for therapeutic use. The existence of cross-talk between AhR and ER causes certain AhR ligands to exert estrogenic endocrine disrupting activity in the absence of binding to ER. Existing methods for studying these mechanisms are cumbersome and time consuming, and for cell-based methods, compound degradation by cellular metabolism significantly affects results. Recently, IA has developed biosensors for studying real-time association and dissociation kinetics between ER-alpha & -beta, and estrogenic nuclear response element (ERE) in the presence of agonists and antagonists. IA proposes to extend this technology to develop chemistries and methods which will allow the biosensors to be applied to study the complex AhR-mediated signaling pathways. During Phase I, biosensors for assessing the interaction of AhR with ligands, accessory proteins, and dioxin response element (DRE) will be developed. During Phase II, biosensors will be used to analyze cross-talk between ER and AhR, and to create screening methods for predicting effects of compounds based on hER & AhR mechanisms. PROPOSED COMMERCIAL APPLICATIONS: Biosensors which allow studying the real-time binding kinetics of compounds (agonists, antagonists, accessory proteins) to the AhR will provide researchers with powerful tools for screening environmental endocrine disruptors and for designing, developing, and testing new pharmaceuticals for treatment of cancer.

了解化合物和药物与芳基烃受体（AHR）和雌激素受体（ER）信号通路相互作用的机制对于鉴定潜在的环境和内分泌干扰物以及用于治疗用途的筛查化合物都很重要。 AHR和ER之间的串扰存在导致某些AHR配体在没有与ER结合的情况下发挥雌激素内分泌的活性。 研究这些机制的现有方法是繁琐且耗时的，对于基于细胞的方法，细胞代谢的复合降解会显着影响结果。 最近，IA开发了用于研究Er-Alpha和-beta和雌激素核反应元件（ERE）之间实时关联和分离动力学的生物传感器，在激动剂和拮抗剂的存在下。 IA建议将这项技术扩展到开发化学和方法，以使生物传感器可以应用于复杂的AHR介导的信号通路。 在第一阶段，将开发用于评估AHR与配体，辅助蛋白和二恶英反应元件（DRE）相互作用的生物传感器。 在II期期间，生物传感器将用于分析ER和AHR之间的串扰，并创建筛选方法，以预测基于HER和AHR机制的化合物的影响。 拟议的商业应用： 允许研究化合物（激动剂，拮抗剂，辅助蛋白）实时结合动力学的生物传感器将为研究人员提供有力的工具，用于筛选环境内分泌干扰物以及设计，开发和测试新的药物以治疗癌症。