Improved NMR Technology for Natural Products and Metabolomics.

描述（由申请人提供）：生物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是非常有效的，因此产量非常低。为了鉴定天然产物，必须获得足够的材料，以便使用质谱（MS）和核磁共振（NMR）光谱对其进行分析表征。质谱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。核磁共振提供了原子水平的信息，可以用来确定未知的结构，但它是非常不敏感的，因此需要大量的样品。本建议旨在提高核磁共振测量的灵敏度，以减少天然产物鉴定的样品要求。最具成本效益和实用的技术改进是核磁共振探针的设计，它提供了样品和光谱仪之间的直接接口。本提案的总体目标是设计、制造、测试和使用一种新的低温冷却探针，该探针采用高温超导（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。结果将是13C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可用的最佳探针的1H质量灵敏度。在这项提议中合作的研究小组之前曾合作建造了一个1毫米高温超导低温冷却探头，该探头目前具有世界上最大的1H质量灵敏度。新的13C优化探针将为高温超导探针提供重大的技术飞跃，并将通过大幅减少样品需求，使许多新的天然产物发现研究成为可能。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的生物体。继续寻找自然产生的化学物质以提供治疗疾病的新方法是至关重要的。这一建议支持技术的发展，以提高从自然界中发现这些重要化学物质的效率。

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.