High Throughput, High Sensitivity NMR

该提案是购买设备，改造曼彻斯特大学（UoM）现有的核磁共振（NMR）光谱仪，使其可用于高通量（HTP）核磁共振，具有高灵敏度检测。仪器所在的曼彻斯特生物技术研究所（MIB）有一个机器人液体处理设备，这对于HTP研究所需的可重复样品制备是必要的。核磁共振光谱可以作为分子指纹，由化学物质的结构精确定义。使用核磁共振来研究分子混合物部分受到灵敏度和（对于1H核磁共振）分辨率的影响。曼彻斯特开发的最先进的方法可以解决部分或全部这些限制。利用复杂的核磁共振技术对复杂混合物进行HTP研究，以提高灵敏度、分辨率和/或特异性，这将允许定义由于代谢（在高等真核生物、介质、水或土壤中）或特定生物催化剂而导致的化学成分变化，或筛选小分子对靶蛋白的影响，无论是作为药物样分子，还是作为赋形剂。此外，我们将继续使用该设备进行结构和功能生物分子核磁共振，研究溶液中的蛋白质。这项研究将对环境和工业生物技术产生影响，使之能够向“净零”碳排放过渡并发展可持续农业，并对生物化学研究产生影响，使之能够开发药物，从而实现终身健康。

This proposal is to purchase equipment to convert an existing Nuclear Magnetic Resonance (NMR) spectrometer at the University of Manchester (UoM) so that it can be used for high-throughput (HTP) NMR with high sensitivity detection.The Manchester Institute of Biotechnology (MIB), where the instrument is housed, has a robotic liquid-handling Facility, necessary for the reproducible sample preparation required for HTP studies. NMR spectra can be used as a molecular fingerprint that is defined precisely by the structure of a chemical. Use of NMR to study mixtures of molecules is compromised partly by sensitivity, and also by (for 1H NMR) resolution. State of the art methodology developed in Manchester can solve some or all of these limitations. HTP studies of complex mixtures using sophisticated NMR techniques to increase sensitivity, resolution and/or specificity will allow definition of changes in chemical composition due to metabolism (in higher eukaryotes, media, water, or soil) or specific biocatalysts, or to screen small molecules for their effects on target proteins, either as drug-like molecules, or excipients. In addition, we will continue to use the equipment for structural and functional biomolecular NMR, to study proteins in solution. The research will impact on environmental and industrial biotechnology, enabling the transition to "net zero" carbon emissions and developing sustainable agriculture, and on biochemical research, enabling pharmaceutical development and consequently life-long health.