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: 8063940
• 负责人: PERIANNAN KUPPUSAMY
• 金额: $ 25.69万
• 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 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8063940
• 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。超氧化物在少量产生时参与细胞信号传导过程。然而，病理过程中大量产生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理解其在正常和病理生理学中的作用至关重要。已经开发了多种分析技术来量化生物系统中的超氧自由基，包括利用超氧化物还原铁细胞色素 c 或硝基蓝四唑的分光光度法；基于化学发光和荧光的技术；和电子顺磁共振（EPR）光谱。然而，许多这些方法对于测量超氧化物具有一定的局限性，主要是缺乏特异性或必要的反应速率。我们已经确定了一类基于三苯甲基自由基的新型探针，用于检测和量化生物系统中产生的超氧化物，与现有探针相比，具有更高的灵敏度和特异性。这些新探针的一个子集是双峰的 - 它们可以通过 EPR 以及荧光显微镜技术进行检测。因此，本提案的目标是开发和表征其他新型三苯甲基探针，用于生物系统中超氧化物的检测和定量，并进一步开发和表征这些探针的双峰子集用于成像应用。因此，提出以下具体目标：(i) 稳定的全氯三苯甲基 (PTM) 衍生的顺磁自旋探针的合成、表征和验证测试，用于生物系统中超氧化物的定量；(ii) 合成、表征和验证测试稳定的双峰全氯三苯甲基 (PTM) 衍生的顺磁自旋探针，用于生物系统中超氧化物分布的定量和荧光成像。该提案的目标是开发和表征新型三苯甲基探针，用于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，超氧化物的产生量很少，并参与细胞信号传导过程。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了解其在正常和病理生理学中的作用至关重要。

项目成果

Perchlorotrityl radical-fluorophore conjugates as dual fluorescence and EPR probes for superoxide radical anion.

全氯三苯甲基自由基-荧光团缀合物作为超氧自由基阴离子的双荧光和 EPR 探针。

• 发表时间: 2010-01-15
• 影响因子: 3.5
• 作者: Wang, Jinhua;Dang, Vinh;Zhao, Wei;Lu, Dongning;Rivera, Brian K;Villamena, Frederick A;Wang, Peng George;Kuppusamy, Periannan
• 通讯作者: Kuppusamy, Periannan