Fluorescent Probes for Manganese(II)

锰(II)荧光探针

• 批准号: 7229855
• 负责人: JAMES W CANARY
• 金额: $ 20.03万
• 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 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7229855
• 关键词: Auditory system; Binding; Biological; Biological Assay; Biomedical Research; Brain; Brain region; Cadmium; Calcium Channel; Cells; Charge; Chemicals; Chemistry; Color; Complement; Complex; Condition; Conductive hearing loss; Cultured Cells; Cytoplasmic Granules; Data; Detection; Development; Dyes; Electrons; Ensure; Fluorescence; Fluorescence Microscopy; Fluorescent Probes; Goals; Image; Image Enhancement; Imaging Techniques; In Vitro; Ions; Link; Literature; Magnetic Resonance Imaging; Manganese; Medical; Medical Research; Metals; Methodology; Methods; Mus; Neurologic; Neurons; Neurosciences; Permeability; Physiological; Procedures; Property; Protocols documentation; Reporter; Research; Research Personnel; Resolution; Role playing therapy; Sampling; Serinus; Slice; Solutions; Standards of Weights and Measures; System; Testing; Time; Tissues; Titrations; Validation; base; biological research; cadmium ion; design; fluorescence imaging; fluorexon; fluorophore; follow-up; improved; interest; medical schools; molecular recognition; novel; novel strategies; programs; research study; stoichiometry; tool; uptake

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（例如 Ca(II)）的荧光探针已被证明是对于生物研究非常有价值的工具，特别是在金属充当化学信使的神经科学中。 “开启荧光”（其中探针发光或改变颜色）比“关闭荧光”（其中荧光被分析物猝灭）更优选。理想的探针应该是比例式的，在一个波长处显示关闭荧光，而在另一波长处显示荧光按比例增加。许多具有生物学意义的顺磁性金属离子，包括 Cu(II)、Fe(II)、Mn(II)、Ni(II)、Co(II) 等只能使用已知探针通过离荧光进行研究，因为它们的不成对电子提供了猝灭荧光的机制。该项目的目标是开发一种新方法，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到Mn(II)的比率荧光滴定。金属 Mn(II) 广泛用作小鼠脑功能的锰增强磁共振成像 (MEMRI) 研究的工具。 Mn(II) 可通过钙通道而不阻塞它们，使其成为神经学研究的独特且有价值的工具。然而，目前还不可能将 Mn(II) 浓度与观察到的对比度直接关联起来，因为没有足够的工具可以做到这一点。因此，本提案中描述的探针将为 MEMRI 研究中所做的假设提供必要的确认。开发荧光检测来补充 MEMRI 技术将允许测试大脑中 Mn(II) 的吸收和释放，测试大脑内的区域定位，并允许识别组织特异性吸收。因此，R21应用的总体目标是通过荧光观察小鼠大脑中Mn(II)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新策略。