Improved NMR Technology for Natural Products and Metabolomics.

改进的天然产物和代谢组学 NMR 技术。

• 批准号: 7700084
• 负责人: ARTHUR S EDISON
• 金额: $ 48.56万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7700084
• 关键词: Benchmarking; Biological; Biological Factors; Biological Testing; Cell Nucleus; Cells; Chemicals; Communicable Diseases; Communication; Databases; Deposition; Detection; Disease; Drug Prescriptions; Drug usage; Frequencies; Funding; Goals; Health; High temperature of physical object; Human; Infection; Ions; Laboratories; Laboratory culture; Life; Liquid substance; Magnetic Resonance Imaging; Malignant Neoplasms; Mass Spectrum Analysis; Measurement; Methods; Microbe; Molecular Weight; NMR Spectroscopy; Nature; Nuclear Magnetic Resonance; Organism; Performance; Pharmaceutical Preparations; Plants; Qualifying; Radio; Relative (related person); Research Personnel; Running; Sampling; Series; Spectrum Analysis; Structure; Techniques; Technology; Testing; Tube; Work; analytical tool; cancer pain; cost; design; functional group; improved; interest; magnetic field; metabolomics; microbial; next generation; novel; performance tests; programs; public health relevance; research study; technology development

DESCRIPTION (provided by applicant): Living organisms produce chemicals called natural products for defense and communication. Oftentimes, these chemicals, or similar derivatives, can be used by humans as drugs, and nearly 50% of all the prescription drugs that are in use today were derived from naturally occurring chemicals. Some of the most interesting and promising natural products are extremely potent and thus are produced in very low amounts. In order to identify natural products, it is necessary to obtain enough material to analytically characterize them using mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. MS is a very sensitive technique, but it often does not provide enough information to fully identify an unknown molecule. NMR provides atomic level information that can be used to determine unknown structures, but it is very insensitive and thus requires a large amount of sample. This proposal seeks to improve the sensitivity of NMR measurements in order to reduce the sample requirements for natural product identification. The most cost-effective and practical technical improvement is in the design of the NMR probe, which provides the direct interface between the sample and the spectrometer. The overall goal of this proposal is to design, build, test, and commission a new cryogenically cooled probe with high temperature superconducting (HTS) material. By improving the technical designs of the coils, this probe will be optimized for 13C detection but will retain exceptional performance for 1H detection as well. The result will be nearly a 10-fold improvement in 13C mass sensitivity over the best currently available probe. It will also have a 1H mass sensitivity that is equal to, or greater than, the best currently available probe. The team of investigators that are collaborating on this proposal have previously worked together to build a 1-mm HTS cryogenically cooled probe, which currently has the greatest 1H mass sensitivity in the world. The new 13C- optimized probe will provide a significant technological leap in HTS probes and will enable many new studies in natural product discovery through large decreases in sample requirements. PUBLIC HEALTH RELEVANCE Many of drugs that humans take to cure diseases, especially cancer and microbial infections, are derived from living organisms. It is critical to continue to search for naturally occurring chemicals to provide new cures to disease. This proposal supports the development of technology to improve the efficiency of discovery of these important chemicals from nature.

描述（由申请人提供）：生物体产生被称为天然产物的化学物质，用于防御和通信。通常，这些化学物质或类似的衍生物可以被人类用作药物，今天使用的所有处方药中有近50%来自天然存在的化学物质。一些最有趣和最有前途的天然产品非常有效，因此产量非常低。为了识别天然产物，有必要获得足够的材料，使用质谱（MS）和核磁共振（NMR）光谱对其进行分析表征。MS是一种非常敏感的技术，但它通常不能提供足够的信息来完全识别未知分子。NMR提供原子水平的信息，可用于确定未知结构，但它非常不敏感，因此需要大量的样品。该提案旨在提高NMR测量的灵敏度，以减少天然产物鉴定的样品要求。最具成本效益和实用性的技术改进是NMR探头的设计，它提供了样品和光谱仪之间的直接接口。该提案的总体目标是设计，建造，测试和调试一种新的低温冷却探头与高温超导（HTS）材料。通过改进线圈的技术设计，该探头将针对13C检测进行优化，但也将保留1H检测的卓越性能。其结果将是13 C质量灵敏度比目前最好的探针提高近10倍。它还将具有等于或大于目前最好的探针的1H质量灵敏度。正在合作研究这一提案的研究人员团队此前曾合作建造了一个1 mm HTS低温冷却探头，该探头目前具有世界上最大的1H质量灵敏度。新的13 C优化探针将提供HTS探针的重大技术飞跃，并将通过大幅降低样品需求来实现天然产物发现的许多新研究。公共卫生相关性人类用于治疗疾病，特别是癌症和微生物感染的许多药物都来自活生物体。继续寻找自然产生的化学物质以提供新的疾病治疗方法至关重要。该提案支持开发技术，以提高从自然界发现这些重要化学品的效率。