In-vivo Drug Interaction of Cytochrome P450 probed by resonant enhanced Coherent anti-Stokes Raman Scattering (CARS) Microscopy

通过共振增强相干反斯托克斯拉曼散射 (CARS) 显微镜探测细胞色素 P450 的体内药物相互作用

• 批准号: 36624835
• 负责人: Dr. Marcel Günther Friedrich
• 金额: --
• 依托单位: Department of Chemistry and Chemical Biology
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 无数据
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/36624835?language=en
• 关键词: vivo; Drug; Interaction; Cytochrome; P450

Cytochromes P450 are NAD(P)H dependent, 6-type heme containing monooxygenases that catalyse a variety of reactions in the human organism. They provide the primary defensive system against xenobiotics, they are involved in the metabolism of more than 80% of all currently used drugs and they are main target in current cancer therapies. The proposed work comprises the development of an in-vivo method to visualize the activity of Cytochrome P450 in living cells. Coherent anti-Stokes Raman scattering microscopy is a novel and powerful tool that overcomes the disadvantages of conventional vibration Spectroscopy. This nonlinear technique utilizes vibrational contrast, which permits rapid and non-invasive in vivo imaging with high chemical sensitivity and selectivity as well as a high threedimensional spatial resolution. The aim of this project is to extend this technique for the first time into the field of heme proteins in order to study pharmacological aspects with clinical relevance on a molecular level, such as the metabolism of drugs, drug interactions, enzyme-ligand interactions or processes occurring during cancer evolution. This will be investigated in detail as a function of different parameters, such as concentrations of different drugs or carcinogens, oxygen content and different cell types. Moreover, the investigation could yield a better understanding of processes related to the evolution of cancer for examples as a consequence of outer factors, such as drugs or chemicals compounds.

细胞色素P450是NAD（P）H依赖性的、含6型血红素的单加氧酶，其催化人类生物体中的多种反应。它们提供了对抗外源性物质的主要防御系统，它们参与了80%以上目前使用的药物的代谢，并且它们是目前癌症治疗的主要靶点。拟议的工作包括开发一种体内方法，以可视化活细胞中细胞色素P450的活性。相干反斯托克斯拉曼散射显微镜是一种新颖而强大的工具，它克服了传统振动光谱学的缺点。这种非线性技术利用振动对比度，它允许快速和非侵入性的体内成像，具有高化学灵敏度和选择性以及高三维空间分辨率。该项目的目的是将该技术首次扩展到血红素蛋白领域，以便在分子水平上研究具有临床相关性的药理学方面，例如药物代谢，药物相互作用，酶-配体相互作用或癌症演变过程中发生的过程。这将作为不同参数的函数进行详细研究，例如不同药物或致癌物的浓度，氧含量和不同细胞类型。此外，这项研究可以更好地了解与癌症演变有关的过程，例如由于外部因素，如药物或化学化合物。