Novel trityl probes for measurement and bi-modal imaging of superoxide

用于超氧化物测量和双模态成像的新型三苯甲基探针

• 批准号: 7631221
• 负责人: PERIANNAN KUPPUSAMY
• 金额: $ 27万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7631221
• 关键词: Aging; Cell Signaling Process; Detection; Electron Spin Resonance Spectroscopy; Fluorescence; Fluorescence Microscopy; Free Radicals; Functional disorder; Goals; Hypertension; Image; Lead; Malignant Neoplasms; Measurement; Measures; Methods; Molecular Probes; Neurodegenerative Disorders; Nitroblue Tetrazolium; Optical Methods; Pathologic Processes; Process; Reperfusion Injury; Role; Sensitivity and Specificity; Specificity; Structure; Superoxides; Techniques; Testing; Tissues; Validation; base; biological systems; cytochrome c; fluorescence imaging; imaging probe; novel; reaction rate

DESCRIPTION (provided by applicant): Superoxide has been implicated in a variety of pathophysiological processes such as ischemia-reperfusion injury, neurodegenerative diseases, hypertension, aging, and cancer. Superoxide, when produced in low amounts, is involved in cell-signaling processes. However, large amounts produced during pathological processes may lead to cellular dysfunction and tissue damage. Hence, the detection of superoxide is critical to our understanding of its role in normal and pathophysiology. A variety of analytical techniques have been developed to quantify superoxide radicals in biological systems including spectrophotometric methods that use the reduction of ferricytochrome c or nitroblue tetrazolium by superoxide; chemiluminescence and fluorescence-based techniques; and electron paramagnetic resonance (EPR) spectroscopy. However, many of these methods have certain limitations for measuring superoxide, primarily lacking specificity or the necessary reaction rates. We have identified a new class of probes based on trityl radicals to detect and quantify superoxide produced in biological systems with greater sensitivity and specificity when compared to existing probes. One subset of these new probes is bi-modal - they can be detected by EPR as well as fluorescence microscopy techniques. Therefore, the goal of this proposal is to develop and characterize additional new trityl-based probes for detection and quantification of superoxide in biological systems, and to further develop and characterize the bi-modal subset of these probes for imaging applications. Accordingly, the following specific aims are proposed: (i) Synthesis, characterization, and validation testing of stable perchloro-triphenylmethyl (PTM)-derived paramagnetic spin probes for quantification of superoxide in biological systems and (ii) Synthesis, characterization, and validation testing of stable, bi-modal perchloro-triphenylmethyl (PTM)-derived paramagnetic spin probes for quantification and fluorescence imaging of superoxide distribution in biological systems. The goal of this proposal is to develop and characterize new trityl-based probes for detection, quantification, and imaging of superoxide in biological systems. Superoxide has been implicated in a variety of pathophysiological processes such as ischemia-reperfusion injury, neurodegenerative diseases, hypertension, aging, and cancer. Under normal circumstances, superoxide is produced in low amounts and is involved in cell-signaling processes. During pathological conditions, large amounts of superoxide may lead to cellular dysfunction and tissue damage. Hence, the detection of superoxide is critical to our understanding of its role in normal and pathophysiology.

描述（由申请人提供）：超氧化物与多种病理生理过程有关，例如缺血 - 再灌注损伤，神经退行性疾病，高血压，衰老和癌症。超级氧化物以低量生产时，会参与细胞信号过程。但是，病理过程中产生的大量可能导致细胞功能障碍和组织损伤。因此，超氧化物的检测对于我们对其在正常和病理生理学中的作用的理解至关重要。已经开发了各种分析技术来量化生物系统中的超氧化物自由基，包括分光光度法方法，这些方法使用超氧化物使用铁染色物C或硝基蓝色四唑仑；化学发光和基于荧光的技术；和电子顺磁共振（EPR）光谱。但是，其中许多方法对测量超氧化物有一定的局限性，主要缺乏特异性或必要的反应速率。与现有探针相比，我们已经确定了基于Trityl自由基的新探针，以检测和量化具有更高敏感性和特异性的生物系统中产生的超氧化物。这些新探针的一个子集是双模式的 - 可以通过EPR和荧光显微镜技术检测到它们。因此，该提案的目的是开发和表征基于新的Trityl的其他新探针，以检测和定量生物系统中的超氧化物，并进一步开发和表征这些探针的双模式子集以进行成像应用。 Accordingly, the following specific aims are proposed: (i) Synthesis, characterization, and validation testing of stable perchloro-triphenylmethyl (PTM)-derived paramagnetic spin probes for quantification of superoxide in biological systems and (ii) Synthesis, characterization, and validation testing of stable, bi-modal perchloro-triphenylmethyl (PTM)-derived paramagnetic自旋探针，用于生物系统中超氧化物分布的定量和荧光成像。该提案的目的是开发和表征基于Trityl的新探针，以检测生物系统中超氧化物的检测，定量和成像。超氧化物与多种病理生理过程有关，例如缺血再灌注损伤，神经退行性疾病，高血压，衰老和癌症。在正常情况下，超氧化物的生产量低，并参与细胞信号过程。在病理条件下，大量的超氧化物可能导致细胞功能障碍和组织损伤。因此，超氧化物的检测对于我们对其在正常和病理生理学中的作用的理解至关重要。