Acquisition of a 600 MHz High-Resolution NMR CryoProbe

俄勒冈州立大学的Victor Hsu博士获得了一笔拨款，为他们的600兆赫核磁共振（NMR）光谱仪购买冷冻探针。核磁共振波谱的独特之处在于它是唯一一种在溶液中产生原子尺度分子信息的技术。自从1995年安装了600兆赫的核磁共振仪器以来，来自俄勒冈州立大学各个院系的研究人员已经使用核磁共振光谱研究了从13C、15n标记的蛋白质- dna复合物到从海藻和啤酒花中分离出来的抗癌/抗肿瘤药物，测量草籽中的油含量，研究大鼠尿液中的代谢物水平。然而，这种仪器广泛使用的限制之一是其固有的敏感性。由于许多项目涉及从自然来源分离或合成获得的生物分子，因此在样品有限的条件下收集有用的核磁共振波谱通常是困难的，如果不是不可能的话。然而，最近研制出的低温探针使仪器的灵敏度提高了四倍。通过将检测线圈和前置放大器的工作温度降低到低温，提高了探头的信噪比。因此，线圈的效率增加，热噪声存在于线圈和前置放大器是减少。这在实际中意味着，通过使用冷冻探针，目前使用的相同实验可以用少4倍的样品进行，或者所需时间减少16倍。在许多研究项目中，将大大受益于核磁共振冷冻探针的灵敏度提高如下：Hsu博士（生物化学/生物物理学）的项目涉及了解环境和内源性损伤对分子功能和相互作用的影响，以及他的抗肿瘤药物dna结合的研究；William Gerwick博士（药学）对海洋蓝藻和藻类生物活性天然产物的结构研究；James White博士和David Horne博士（化学）对合成方法和生物活性天然产物和其他复杂分子的全合成的研究；李开昌博士（林产）木质素真菌降解机制研究；Max Deinzer博士（化学）对蛋白质烷基化和/或氧化如何影响蛋白质折叠途径的研究。随着低温探针的到来和安装，许多样品和灵敏度有限的项目将由同一研究人员和其他人发起。如果没有冷冻探针，这些新项目中的大多数都是不可能的。利用现有600兆赫核磁共振光谱仪的主要参与的研究项目已经导致了四十多篇同行评议的期刊文章，评论文章和书籍章节，以及更多的在地方，国家和国际科学会议上的演讲。同样重要的是，徐博士对核磁共振仪器对大学基础设施的影响感到特别满意。这个光谱仪已经被俄勒冈州立大学校园里的十几个研究小组的成员和其他机构的其他用户使用。这些用户包括本科生和研究生、博士后助理和主要研究人员。这一工具也非常成功地用于课堂教学和直接针对吸引妇女和少数民族学生参加科学课程的方案。事实上，女性和少数族裔科学家占接受过使用该仪器培训的研究人员的一半以上。其他项目针对的是初高中水平的学生，其中一些学生已经获得了涉及使用核磁共振仪器的暑期研究工作。完全可以预见，冷冻探针将加强和增加这些培训、研究和推广活动，核磁共振仪器将继续成为俄勒冈州立大学校园和西北地区高度重视和利用的研究资源。

A grant has been award to Dr. Victor Hsu at Oregon State University to acquire a cryoprobe for their 600 MHz nuclear magnetic resonance (NMR) spectrometer. NMR spectroscopy is unique in that it is the only technique that yields molecular information at the atomic scale in solution. Since the installation of the 600 MHz NMR instrument in 1995, researchers from various Departments and Colleges on the Oregon State University campus have used NMR spectroscopy to study samples ranging from 13C,15N-labeled protein-DNA complexes to anticancer/antitumor agents isolated from marine algae and beer hops to measuring oil content in grass seeds to studying metabolite levels in rat urine. However, one of the limitations to the wider use of this instrument has been its inherent sensitivity. Since many of the projects involve biomolecules that are either isolated from natural sources or are synthetically obtained, collecting useful NMR spectra under sample-limited conditions is often difficult, if not impossible. Recently, however, cryogenic probes have been developed that improve the sensitivity of the instrumentation by a factor of four. The improved signal to noise (S/N) ratio of these probes is obtained by reducing the operating temperature of the detection coil and the pre-amplifier to cryogenic temperatures. Thus the efficiency of the coil is increased and the thermal noise present in the coil and the pre-amplifier is reduced. What this means in practical terms is that by using cryoprobes, the same experiments that are currently used can be performed with either four times less sample, or a 16-fold reduction in the amount of time required. Among the many research projects that would greatly benefit from the increased sensitivity of the NMR cryoprobe are the following: Dr. Hsu's (Biochemistry/Biophysics) projects involving understanding the effects of environmental and endogenous damage on molecular function and interactions, and his studies of DNA-binding by antitumor drugs; Dr. William Gerwick's (Pharmacy) structural studies of biologically-active natural products from marine cyanobacteria and algae; Dr. James White's and Dr. David Horne's (Chemistry) studies of synthetic methods and the total synthesis of biologically-active natural products and other complex molecules; Dr. Kaichang Li's (Forest Products) investigations into the mechanisms of fungal degradation of lignin; and Dr. Max Deinzer's (Chemistry) studies into how protein alkylation and/or oxidation affects protein folding pathways. With the arrival and installation of the cryoprobe, many sample- and sensitivity-limited projects will be initiated, both by the same researchers and others. Most of these new projects would be impossible without the cryoprobe. Research projects utilizing a major involvement of the existing 600 MHz NMR spectrometer have led to more than forty peer - reviewed journal articles, review articles, and book chapters, and an even greater number of presentations at local, national, and international scientific meetings. Of equal importance, Dr. Hsu is especially pleased with the impact the NMR instrumentation has had on the University's infrastructure. This spectrometer has been used by members of over a dozen research groups on the OSU campus and additional users from other institutions. These users have included undergraduate and graduate students, postdoctoral associates and principal investigators. This instrument has also been very successfully utilized for teaching in classroom settings and in programs directly targeted to attracting women and minority students into the science curriculum. In fact, women and minority scientists represent more than half of the researchers trained to use the instrument. Other programs identify students at the middle and high school level, and several of these students have gained summer research employment involving the use of the NMR instrumentation. It is fully anticipated that the cryoprobe will enhance and increase these training, research, and outreach activities, and that the NMR instrument will continue to be a highly valued and utilized research resource on the OSU campus and in the Northwest region.