Acquisition of a High Frequency Pulsed Electron Spin Resonance Spectrometer

获得高频脉冲电子自旋共振谱仪

• 批准号: 7827737
• 负责人: SUNIL K SAXENA
• 金额: $ 162.35万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7827737
• 关键词: Appointment; Behavior; Biocompatible Materials; Biology; Charge; Chemicals; Chemistry; DNA-Protein Interaction; Drug Delivery Systems; Electron Spin Resonance Spectroscopy; Electron Transport; Electrons; Frequencies; Funding; Funding Applicant; Grant; Ions; Measurement; Membrane Proteins; Metals; Microscopic; Molecular Structure; Monitor; Neurodegenerative Disorders; Nuclear; Nuclear Magnetic Resonance; Physiologic pulse; Process; Protein Dynamics; Proteins; Reaction; Research Personnel; Resolution; Sampling; Science; Seeds; Structure; Structure-Activity Relationship; Synthesis Chemistry; System; TNFRSF5 gene; United States National Institutes of Health; Universities; Work; X ray diffraction analysis; X-Ray Diffraction; drug discovery; innovation; instrument; macromolecule; medical schools; nanometer; protein structure; research study; tool

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.

描述（由申请人提供）：要求购买Bruker Elexsys E680 ft/cw光谱仪的资金。光谱仪将在Pitt建立高级电子自旋共振（ESR）设施，并最初将为九个研究人员提供服务（Curran，Jen-Jacobson，Klein-Seetharaman，Saxena，Saxena，Schafmeister，Schafmeister，Trakselis，Waldeck，Witzel和Wipf）。 NIH赠款类型（包括P01，P50，R01和R37（功绩））支持了七个用户。研究人员的主要任命是化学（Curran，Saxena，Trakselis，Waldeck，Wipf），生物学（Jen-Jacobson）和匹兹堡大学的医学院（Klein-Seetharaman，Wetzel）以及化学学院的化学（Schafmeister）（Schafmeister）。这些研究者中有几个合作着阐明膜蛋白和低聚蛋白中结构功能关系的关系。许多这些系统的宏观行为的显微镜起源无法使用常规结构工具（例如核磁共振或X射线衍射）轻松理解。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）允许对蛋白质和大分子中快速动态的敏感测量； （b）实现生物分子中纳米范围距离的高分辨率测量，以确定对大分子结构和构象动力学的约束； （c）允许测量电子核距离，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传输和电荷转移过程； （e）为瞬时自由基的身份提供增强的分辨率，以阐明有机反应机制。用户组需要更多的高端脉冲ESR实验能力，访问高频ESR实验以及对浓度有限样品的更灵敏度 - 这些需求决定了所需的仪器。化学系将提供175,000美元作为购买光谱仪的匹配资金，并在雪佛龙科学中心（化学部）进行翻新和配置适合光谱仪的空间。生物医学相关性：光谱仪将支持几个具有强大生物医学相关性的项目。其中包括对几种有吸引力的药物靶标的结构的测量和构象动力学，对与神经退行性疾病有关的几种蛋白质折叠，蛋白-DNA相互作用的一般原理的建立以及针对药物发现的创新合成化学。

项目成果

Origins of structural flexibility in protein-based supramolecular polymers revealed by DEER spectroscopy.

• DOI: 10.1021/jp505643w
• 发表时间: 2014-08-21
• 期刊: The journal of physical chemistry. B
• 作者: Tavenor NA;Silva KI;Saxena S;Horne WS
• 通讯作者: Horne WS

Cu(II)-Zn(II) Cross-Modulation in Amyloid-Beta Peptide Binding: An X-ray Absorption Spectroscopy Study.

• DOI: 10.1021/acs.jpcb.5b10264
• 发表时间: 2015-12-31
• 期刊: The journal of physical chemistry. B
• 作者: De Santis E;Minicozzi V;Proux O;Rossi G;Silva KI;Lawless MJ;Stellato F;Saxena S;Morante S
• 通讯作者: Morante S

Cysteine-specific Cu2+ chelating tags used as paramagnetic probes in double electron electron resonance.

在双电子电子共振中用作顺磁探针的半胱氨酸特异性 Cu2+ 螯合标签。

• DOI: 10.1021/jp5103143
• 发表时间: 2015-02-19
• 期刊: The journal of physical chemistry. B
• 作者: Cunningham TF;Shannon MD;Putterman MR;Arachchige RJ;Sengupta I;Gao M;Jaroniec CP;Saxena S
• 通讯作者: Saxena S

Insights into copper coordination in the EcoRI-DNA complex by ESR spectroscopy.

• DOI: 10.1080/00268976.2014.934313
• 发表时间: 2014-12-01
• 期刊: Molecular physics
• 影响因子: 1.7
• 作者: Ji M;Tan L;Jen-Jacobson L;Saxena S
• 通讯作者: Saxena S

The double-histidine Cu²⁺-binding motif: a highly rigid, site-specific spin probe for electron spin resonance distance measurements.

• DOI: 10.1002/anie.201501968
• 发表时间: 2015-05-18
• 期刊: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
• 影响因子: 16.6
• 作者: Cunningham, Timothy F.;Putterman, Miriam R.;Desai, Astha;Horne, W. Seth;Saxena, Sunil
• 通讯作者: Saxena, Sunil