Fluorescent Probes for Manganese(II)

锰(II)荧光探针

• 批准号: 7018591
• 负责人: JAMES W CANARY
• 金额: $ 17.87万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7018591
• 关键词: animal tissue; bioimaging /biomedical imaging; brain imaging /visualization /scanning; brain metabolism; cadmium; fluorescence microscopy; fluorescent dye /probe; imaging /visualization /scanning; ionophores; magnetic resonance imaging; manganese; membrane permeability; technology /technique development; tissue /cell culture

DESCRIPTION (provided by applicant): Fluorescent probes for metal ions such as Ca(ll) have proven to be tremendously valuable tools for biological research, particularly in neuroscience where metals play roles as chemical messengers. "On- fluorescence," where the probe lights up or changes color, is greatly preferred to "off-fluorescence", where fluorescence is quenched by the analyte. The ideal probe would be ratiometric, showing off-fluorescence at one wavelength and proportionate increase in fluorescence at another wavelength. Many biologically interesting metal ions that are paramagnetic including Cu(ll), Fe(ll), Mn(ll), Ni(ll), Co(ll) and others can only be studied by off-fluorescence using known probes because their unpaired electrons provide a mechanism to quench fluorescence. The goal of this project is to develop a new approach that allows on-fluorescence detection of paramagnetic metal ions. In preliminary experiments, ratiometric fluorescence titration of Mn(ll) was observed under solution conditions similar to physiological. The metal Mn(ll) is used widely as a tool in manganese-enhanced magnetic resonance imaging (MEMRI) studies of brain function in mice. Mn(ll) passes calcium channels without blocking them, making it a unique and valuable tool for neurological research. However, it has not yet been possible to correlate Mn(ll) concentrations directly with observed contrast as no adequate tool is available to do so. The probes described in this proposal would thus provide needed confirmation of assumptions made in MEMRI research. Development of a fluorescence assay to complement MEMRI techniques would allow the test Mn(ll) uptake and release in the brain, test for regional localization within the brain, and allow identification of tissue-specific uptake. Thus, the overall goal of this R21 application is to observe Mn(ll) distribution in mouse brain by fluorescence, providing a powerful new tool for neurological research, and demonstrating a useful new strategy that can be applied broadly in biomedical research.

描述（由申请人提供）：金属离子（如Ca（II））的荧光探针已被证明是生物学研究中非常有价值的工具，特别是在金属作为化学信使的神经科学中。其中探针发光或改变颜色的“开荧光”比其中荧光被分析物猝灭的“关荧光”更优选。理想的探针将是比率式的，在一个波长处显示关闭荧光，在另一个波长处显示成比例的荧光增加。许多生物学上感兴趣的顺磁性金属离子，包括Cu（II）、Fe（II）、Mn（II）、Ni（II）、Co（II）等，只能使用已知的探针通过关闭荧光来研究，因为它们的未配对电子提供了淬灭荧光的机制。该项目的目标是开发一种新的方法，允许顺磁性金属离子的荧光检测。在初步实验中，在类似于生理的溶液条件下观察Mn（II）的比率荧光滴定。金属Mn（II）被广泛用作小鼠脑功能的锰增强磁共振成像（MEMRI）研究中的工具。Mn（II）通过钙通道而不阻断它们，使其成为神经学研究的独特而有价值的工具。然而，还不可能将Mn（II）浓度与观察到的对比度直接关联，因为没有足够的工具可用于这样做。因此，本提案中描述的探测器将为MEMRI研究中的假设提供必要的确认。开发荧光测定以补充MEMRI技术将允许测试Mn（II）在脑中的摄取和释放，测试脑内的区域定位，并允许鉴定组织特异性摄取。因此，该R21应用的总体目标是通过荧光观察Mn（II）在小鼠脑中的分布，为神经学研究提供强大的新工具，并展示可广泛应用于生物医学研究的有用的新策略。