Acquisition of a Continuous Wave X-band EPR Spectrometer

描述(由申请人提供)：科罗拉多大学博尔德分校化学和生物化学系迫切需要用现代仪器取代老化、不可靠、过时的电子顺磁共振(EPR)光谱仪。博尔德目前还没有这样的仪器。本提案要求提供资金，以购置一台新的连续波X波段电子顺磁共振光谱仪(Bruker EleXsys E500)，该光谱仪将由八名或更多高影响力研究人员组成的不同小组使用，并将安置在部门共用仪器设施内并进行维护。研究应用：一台EPR光谱仪对于NIH资助的四个主要用户和多个次要用户的研究是必不可少的。大多数应用将利用强大的定点定向自旋标记EPR方法来解决大分子结构、动力学、稳定性或功能的基本问题。其他应用将集中在顺磁性金属蛋白中心、纳米材料和聚合物的表征上。所要求的仪器对于正在进行的研究和新的研究是必不可少的，这些研究集中在：主要用户-蛋白激酶开关和骨架运动的动力学(Natalie Ahn)-膜结合受体、信号蛋白质和多蛋白质信号复合体的结构和机制(Joseph Falke)-高浓度蛋白质药物中的蛋白质-蛋白质相互作用(Theodore Randolph)-细菌外膜生物发生中的蛋白质折叠机制(Marcelo Sousa)。典型的次要用户--用于检测细胞内金属的新型生物传感器中的金属结合和配位(Amy Palmer)--新近发现的RNA开关的结构和动力学(Arthur Pardi)--用于磁共振成像的新型纳米磁性造影剂的自旋系统参数(Stephen Russeck)--新聚合物中稳定的有机自由基的结构(Josef Michl)。所要求的EPR光谱仪将通过以下两方面对公众健康产生积极影响：1)进一步研究与癌症、细菌感染和免疫反应有关的基本细胞信号过程；2)使侧重于蛋白质药物开发和改进核磁共振成像方法的应用研究成为可能。

DESCRIPTION (provided by applicant): The Department of Chemistry and Biochemistry at the University of Colorado, Boulder has a critical need to replace an aging, unreliable, obsolete Electron Paramagnetic Resonance (EPR) spectrometer with a modern instrument. No such instrument currently exists in Boulder. The present proposal requests funding to acquire a new continuous wave X-band EPR spectrometer (Bruker EleXsys E500) that will be utilized by a diverse group of eight or more high impact researchers, and will be housed and maintained within the departmental shared instrumentation facilities. Research applications: An EPR spectrometer is essential for the NIH-funded research of four major users, and multiple minor users. Most applications will utilize powerful site-directed spin-label EPR methods to address fundamental issues of macromolecular structure, dynamics, stability, or function. Other applications will focus on the characterization of paramagnetic metalloprotein centers, nanomaterials, and polymers. The requested instrument is essential for ongoing and new research focusing on: MAJOR USERS - Dynamics of on/off switching and backbone motions in protein kinases (Natalie Ahn) - Structures and mechanisms of membrane-bound receptors, signaling proteins, and multi-protein signaling complexes (Joseph Falke) - Protein-protein interactions at high concentrations of protein pharmaceuticals (Theodore Randolph) - Mechanisms of protein folding in bacterial outer-membrane biogenesis (Marcelo Sousa). REPRESENTATIVE MINOR USERS - Metal binding and coordination in new biosensors designed to detect intracellular metals (Amy Palmer) - Structures and dynamics of recently discovered RNA switches (Arthur Pardi) - Spin system parameters of novel nanoparticle magnetic contrast agents for magnetic resonance imaging (Stephen Russeck) - Structures of stable organic radicals in new polymers (Josef Michl). The requested EPR spectrometer will positively impact public health both by 1) furthering basic research on fundamental cellular signaling processes involved in cancer, bacterial infection and the immune response, and by 2) enabling applied research focusing on protein pharmaceutical development and improvements to MRI imaging methods.