600 MHz NMR Instrument Upgrade at Northwestern University

申请资金用于更换西北大学生物核磁共振中心的高分辨率600 MHz核磁共振光谱仪的控制台，这是一个独特的资源，为结构和化学生物学家提供了在单一设施内进行跨学科研究的高场仪器。自1990年以来，在支持下 从NIH和NSF，西北大学的研究人员已经建立和维护了一个出色的大分子核磁共振资源，这对学院和整个大学内的多名研究人员的研究计划产生了重要的积极影响。600 MHz光谱仪是该设施中唯一的核磁共振仪器，大量且持续使用。然而，由于与老化的控制台有关的一系列问题(包括最持久的FIFO下溢错误问题)，该仪器的可靠性最近有所下降，该控制台上一次更换是在1999年。购买新的控制台以及用于冷探头的替换压缩机(又名冷组)将满足用户对核磁共振时间的巨大需求，该用户群由七个资金充足的主要研究小组组成，致力于生物学或化学-生物学界面上的各种基础和临床问题。正在研究的课题包括转录因子的结构-功能分析，感染剂的结构和功能基因组学，通过蛋白质-蛋白质相互作用进行的电子转移，天然产物的结构表征，运动蛋白调节的结构生物学，用于磁共振成像和诊断应用的新型抑制剂和造影剂的设计和开发，以及用于医学应用的新型合成化学方法。这些项目有很强的结构和/或功能重点，所有这些项目都将受益于增加的敏感性(主要是过去十年在硬件方面的改进)，但最重要的是，新的控制台和冷探头压缩机提供了更高的可靠性。提出的仪器将具有执行任何当代生物分子核磁共振脉冲序列实验的所有能力。由于磁铁和冷探头(压缩机除外)已被确定状态良好，因此没有计划更换它们中的任何一个。新的控制台将有四个通道，第一个通道用于1H激发、去耦合和检测，第二个通道用于生物相关异核的激发、去耦合和宽带检测，一个双通道用于生物相关异核的激发和去耦合，以及脉冲场梯度附件。

DESCRIPTION (provided by applicant): Funding is requested for replacing the console of a high-resolution 600 MHz NMR spectrometer at Northwestern University's Biological NMR Center, a unique resource providing structural and chemical biologists access to high-field instrumentation within a single facility for inter- disciplinary research. Since 1990, with support from NIH and NSF, Northwestern researchers have established and maintained an outstanding resource for macromolecular NMR that has had a significant positive impact on the research programs of multiple investigators both within the college and the university at large. The 600 MHz spectrometer, which is the one and only NMR instrument in the facility, is heavily and continuously used. However, the reliability of this instrument has decreased lately because of a range of problems (including a most persistent FIFO underflow error problem) associated with an aging console, which was last replaced in 1999. The acquisition of a new console along with a replacement compressor (aka cold pack) for the cold probe would cater to the heavy demand for NMR time by a user base that comprises seven well-funded major research groups working on a variety of basic and clinical problems in biology or at the chemistry-biology interface. The research topics being studied include structure-function analyses of transcription factors, structural and functional genomics of infectious agents, electron transfer via protein-protein interactions, structural characterization of natural products, structural biology of kinesin regulation, design and development of novel inhibitors and contrast agents for magnetic resonance imaging and diagnostic applications, and novel synthetic chemistry approaches for medicinal applications. The projects have strong structural and/or functional foci and all of them will benefit from the added sensitivity (mainly from improvements in hardware that have occurred in the past decade), but most significantly, added reliability afforded by a new console and cold probe compressor. The proposed instrument will have all the capabilities to perform any contemporary biomolecular NMR pulse sequence experiment. Since the magnet and cold probe (other than the compressor) have been determined to be in good shape, there are no plans to replace either of them. The new console will have four channels with the first channel for 1H excitation, decoupling and detection, a second channel for excitation, decoupling and broadband detection of biologically-relevant heteronuclei, and a dual channel for excitation and decoupling of biologically-relevant heteronuclei, and pulsed field gradient accessories.