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。该光谱仪将为在皮特建立先进的电子自旋共振(ESR)设施提供种子，并将首先为9名调查人员(Curran、Jen-Jacobson、Klein-Setharaman、Saxena、Schafmeister、Trakselis、Waldeck、Wetzel和Wipf)提供服务。其中7个用户由NIH拨款类型支持，包括P01、P50、R01和R37(优点)。调查人员的主要任命是匹兹堡大学的化学(Curran，Saxena，Trakselis，Waldeck，Wipf)，生物学(Jen-Jacobson)和医学院(Klein-Setharaman，Wetzel)，以及坦普尔大学(Temple University)的化学(Schafmeister)。这些研究人员中的几个人共同致力于阐明膜蛋白和寡聚体蛋白的结构-功能关系。使用核磁共振或X射线衍射等传统结构工具，很难理解其中许多系统宏观行为的微观起源。该光谱仪将用于确定蛋白质的结构和动力学，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)能够对生物分子中的纳米距离进行高分辨率测量，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，以揭示大分子中金属-离子的配位；(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分辨，以阐明有机反应机理。用户组需要更多的容量用于高端脉冲ESR实验，访问高频ESR实验，以及对浓度有限的样品具有更高的灵敏度-这些需求决定了所要求的仪器。化学部将提供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(化学部)为光谱仪翻新和配置合适的空间。生物医学相关性：光谱仪将支持几个与生物医学相关性很强的项目。这些包括对几种有吸引力的药物靶标的膜蛋白的结构和构象动力学的测量，对与神经退行性疾病有关的几种蛋白质的错误折叠，建立蛋白质-DNA相互作用的一般原理，以及针对药物发现的创新合成化学。

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.