Acquisition of a High Frequency Pulsed Electron Spin Resonance Spectrometer

描述（由申请人提供）：申请购买Bruker ElexSys E680 FT/CW光谱仪的资金。光谱仪将为皮特建立先进的电子自旋共振（ESR）设施提供种子，最初将为9名研究人员（Curran，Jen-Jacobson，Klein-Seetharaman，Saxena，Schafmeister，Trakselis，沃尔德克，Wetzel和Wipf）提供服务。其中七个用户得到了NIH资助类型的支持，包括P01，P50，R 01和R37（MERIT）。研究者的主要任命是在匹兹堡大学的化学（Curran，Saxena，Trakselis，沃尔德克，Wipf），生物学（Jen- Jacobson）和医学院（Klein-Seetharaman，Wetzel）以及坦普尔大学的化学（Schafmeister）。这些研究人员中的一些人合作研究膜蛋白和寡聚蛋白的结构-功能关系。许多这些系统的宏观行为的微观起源不能很容易地使用传统的结构工具，如核磁共振或X射线衍射理解。光谱仪将用于确定蛋白质结构和动力学，以及化学和生物材料中的电子转移过程。高频光谱仪将：（a）能够灵敏地测量蛋白质和大分子中的快速动力学;（B）能够高分辨率地测量生物分子中的纳米范围距离，以确定对大分子结构和构象动力学的限制;（c）能够测量电子-核距离，以揭示大分子中的金属-离子配位;（d）监测化学和生物材料中的电子转移和电荷转移过程;以及（e）能够提高对瞬时自由基的识别的分辨率，以阐明有机反应机制。用户组需要更多的高端脉冲ESR实验容量，获得高频ESR实验，以及对浓度受限样品的更高灵敏度-这些需求决定了所需的仪器。化学系将提供17.5万美元作为购买光谱仪的配套资金，并在雪佛龙科学中心（化学系）为光谱仪改造和配置合适的空间。生物医学相关性：光谱仪将支持几个具有强烈生物医学相关性的项目。这些包括测量的结构和构象动力学的几种膜蛋白，有吸引力的药物靶点，错误折叠的几种蛋白质参与神经退行性疾病，建立蛋白质-DNA相互作用的一般原则，以及创新的合成化学药物发现。

DESCRIPTION (provided by applicant): Funds for the purchase of a Bruker ElexSys E680 FT/CW spectrometer are requested. The spectrometer will seed the establishment of an advanced electron spin resonance (ESR) facility at Pitt, and will initially serve a group of nine investigators (Curran, Jen-Jacobson, Klein- Seetharaman, Saxena, Schafmeister, Trakselis, Waldeck, Wetzel, and Wipf). Seven of the users are supported by NIH grant types including P01, P50, R01, and R37 (MERIT). The primary appointments of the investigators are in Chemistry (Curran, Saxena, Trakselis, Waldeck, Wipf), Biology (Jen- Jacobson) and in the Medical School (Klein-Seetharaman, Wetzel) at the University of Pittsburgh, and in Chemistry (Schafmeister) at Temple University. Several of these investigators work collaboratively on the elucidation of structure-function relationships in membrane proteins and oligomeric proteins. The microscopic origins of macroscopic behavior of many of these systems cannot be easily understood using conventional structural tools, such as nuclear magnetic resonance or X-Ray diffraction. The spectrometer will be used to determine protein structure and dynamics, as well as electron transfer processes in chemical and biological materials. The high frequency spectrometer will: (a) allow sensitive measurement of fast dynamics in proteins and macromolecules; (b) enable high resolution measurement of nanometer range distances in biomolecules in order to determine constraints on macromolecular structure and conformational dynamics; (c) allow measurement of electron-nuclear distances in order to reveal metal-ion coordination in macromolecules; (d) monitor electron transfer and charge transfer processes in chemical and biological materials; and (e) enable enhanced resolution to the identity of transient radicals in order to elucidate organic reaction mechanisms. The user group requires more capacity for high-end pulsed ESR experiments, access to high frequency ESR experiments, as well as more sensitivity for concentration limited samples - these needs dictate the requested instrument. The Department of Chemistry will provide $175,000 as matching funds for the purchase of the spectrometer, as well as renovate and configure suitable space for the spectrometer in the Chevron Science Center (Chemistry Department). Biomedical Relevance: The spectrometer will support several projects that have strong biomedical relevance. These include the measurement of structure and conformational dynamics of several membrane proteins that are attractive drug targets, misfolding of several proteins implicated in neurodegenerative diseases, establishment of the general principles of protein-DNA interaction, as well as innovative synthetic chemistry directed towards drug discovery.