Purchase of a Cryo-Probe to Upgrade a 500 MHz NMR System for BioNMR Applications

购买冷冻探针来升级 500 MHz NMR 系统以用于 BioNMR 应用

• 批准号: 7591326
• 负责人: Om Prakash
• 金额: $ 31.61万
• 依托单位: KANSAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7591326
• 关键词: Alzheimer' s Disease; Amyloid beta-Protein; Arts; Ataxia; Binding; Biomedical Research; Biomolecular Nuclear Magnetic Resonance; Carbon; Chitin; Collaborations; Cystic Fibrosis; Data; Dementia; Detection; Disease; Disease Vectors; Distant; Funding; Glucans; Health; Hour; Human; Immunity; Inflammatory; Insect Proteins; Insecta; Institution; Ischemia; Kansas; Lysine; N.I.H. Research Support; Noise; Nucleocapsid Proteins; Peptides; Performance; Proteins; Protons; Research Personnel; Research Project Grants; SARS coronavirus; Sampling; Signal Transduction; Sodium Chloride; Solubility; Solutions; Structure; System; Tertiary Protein Structure; Time; United States National Institutes of Health; Universities; cryogenics; human disease; improved; instrument; instrumentation; programs; public health relevance; research study

DESCRIPTION (provided by applicant): The Kansas State University (KSU) Biomolecular NMR Facility, which has served more than 23 separate NIH-funded research projects, request funding to purchase a 5 mm triple resonance cryogenic probe with enhanced carbon sensitivity and salt tolerant proton coil for an existing Varian 500 NMR System(R) . This acquisition of a cryogenic probe will afford a 2-3 fold enhancement in sensitivity compared with conventional probes and will be of great use to eight major users and many other NIH supported investigators at this campus studying mass-limited biomolecules having less stability and/or low solubility and biomacromolecules that show concentration-dependent aggregation. Currently our users are constrained with the present instrumentation due to the limited sensitivity of the conventional probe. Many of our local researchers supported by NIH funding are forced to go to distant facilities for 2D and 3D NMR studies on their diluted samples, as our 500 MHz NMR spectrometer equipped with a conventional probe is limited in its ability to perform these experiments in a timely manner and in some cases not at all. The cryogenic probe is essential for our 500 MHz console to perform long hours 2D and 3D NMR experiments for studying solution structure and dynamics of large biomolecules and other compounds available in limited amount. The leading performance benefits of the upgraded 500 MHz NMR spectrometer with the requested cryogenic probe will be: a) improved signal-to-noise ratio in the NMR spectra, b) reduced experimental time for multi-dimensional NMR experiments, c) lowered detection limit, and d) enhanced capability to acquire NMR data on diluted samples and on biomacromolecules with low solubility and or less stability. In brief this upgrade will facilitate KSU Biomolecular NMR facility in performing multi-dimensional NMR experiments on proteins/peptides and other biomacromolecules available in low concentration with best possible sensitivity on the existing instrument. The funding of this project will provide a shared instrumentation necessary to complete on going NIH supported research programs at KSU and to elevate inter-institutional biomedical research collaborations between KSU NMR facility and nearby institutions. PUBLIC HEALTH RELEVANCE: Most of the research projects in this application aim at understanding the structure and function of a variety of protein domains relevant to human health. These include chitin binding domain and 2-1, 3 glucan binding domain of insect proteins, lysine-rich domain of the SARS- CoV nucleocapsid protein, channel forming peptides, amyloid beta peptides and biophysical mechanism of protein-protein or protein-peptide interactions, particularly in immunity and inflammatory diseases and in insects as disease vectors. The acquisition of a state-of-the-art cryogenic probe for our existing 500 MHz NMR console will significantly enhance or create new feasibility of such studies of broad importance in a number of human diseases, such as Alzheimer's dementia, ataxia, ischemia, and cystic fibrosis. .

描述（由申请人提供）：堪萨斯州立大学（KSU）生物分子核磁共振设施，已经为超过23个独立的美国国立卫生研究院资助的研究项目提供服务，请求资助为现有的瓦里安500核磁共振系统(R)购买具有增强碳敏感性和耐盐质子线圈的5mm三共振低温探针。与传统探针相比，低温探针的获得将提供2-3倍的灵敏度提高，并将对8个主要用户和许多其他NIH支持的研究人员在该校园研究稳定性和/或溶解度较低的质量有限的生物分子和显示浓度依赖性聚集的生物大分子有很大的用处。目前，由于传统探针的灵敏度有限，我们的用户受到现有仪器的限制。许多由美国国立卫生研究院资助的本地研究人员被迫前往遥远的设施对稀释后的样品进行2D和3D核磁共振研究，因为我们的500 MHz核磁共振光谱仪配备了传统探针，其及时执行这些实验的能力有限，在某些情况下根本无法进行这些实验。低温探针对于我们的500 MHz控制台执行长时间的2D和3D NMR实验至关重要，用于研究大生物分子和其他有限数量的化合物的溶液结构和动力学。配备低温探针的升级版500 MHz核磁共振光谱仪的主要性能优势将是：a)提高核磁共振波谱的信噪比，b)减少多维核磁共振实验的实验时间，c)降低检测限，d)增强在稀释样品和低溶解度或稳定性较差的生物大分子上获取核磁共振数据的能力。简而言之，此次升级将有助于KSU生物分子核磁共振设备在现有仪器上以最佳灵敏度对低浓度的蛋白质/肽和其他生物大分子进行多维核磁共振实验。该项目的资金将提供必要的共享仪器，以完成正在进行的NIH支持的KSU研究项目，并提升KSU核磁共振设备与附近机构之间的机构间生物医学研究合作。公共健康相关性：本应用程序中的大多数研究项目旨在了解与人类健康相关的各种蛋白质结构域的结构和功能。这些包括昆虫蛋白的几丁质结合域和2- 1,3葡聚糖结合域，SARS- CoV核衣壳蛋白的赖氨酸丰富域，通道形成肽，淀粉样肽和蛋白质-蛋白质或蛋白质-肽相互作用的生物物理机制，特别是在免疫和炎症性疾病以及作为疾病媒介的昆虫中。为我们现有的500 MHz核磁共振控制台获得最先进的低温探针将显着增强或创造新的可行性，这些研究在许多人类疾病中具有广泛的重要性，如阿尔茨海默氏痴呆症，共济失调，缺血和囊性纤维化。