Realignment of a 600 MHz NMR system for cellular applications and antibiotic development

重新调整 600 MHz NMR 系统，用于细胞应用和抗生素开发

• 批准号: 497967936
• 金额: --
• 依托单位: Heinrich-Heine-Universität Düsseldorf
• 依托单位国家: 德国
• 项目类别: Major Research Instrumentation
• 财政年份: 2022
• 资助国家: 德国
• 起止时间: 2021-12-31 至 无数据
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/497967936?language=en
• 关键词: Realignment; 600; MHz; NMR; system

The main goal of the project is to make the outstanding properties of fluorine atoms (19F) available for NMR-based structural investigations for the research groups at HHU. The measure therefore represents an essential application extension of the Biomolecular NMR Center, which has been in existence since 2004, and will enable high-resolution insights into cellular systems as well as significantly more efficient antibiotic development. Currently, there is no adequate possibility at HHU to use 19F nuclear spins in biological macromolecules and in living systems. However, a steadily growing body of research from other NMR centers confirms the broad applicability and tremendous scientific utility of 19F nuclear spin. The real benefit of the 19F detection technique stems from the fact that fluorine atoms, on the one hand, have very good NMR properties (100% occurrence of the NMR active isotope, high signal strength and strong dependence of the NMR frequency on the chemical environment). Furthermore, 19F is present only in negligible amounts in biological systems, such as eukaryotic cells. However, there are numerous ways to specifically label molecules with 19F. This allows, for example, highly sensitive and high-resolution NMR studies of 19F-labeled molecules of their native cellular environment, since virtually no background signal emanates from the cell. This is not the case for the regular NMR active nuclei of biological systems (1H, 13C, 15N, 31P). Therefore, concrete planned 19F-NMR applications include the investigation of the structure and dynamics of neuropeptides, G-protein coupled receptors, and DNA-mediated catalysis using so-called in-cell NMR methods. In addition, in-cell NMR will be further developed by using not only isolated cells but also, for the first time, so-called three-dimensional organoids, such as brain organoids.In addition to in-cell NMR, 19F NMR spectroscopy also offers unique possibilities for in vitro investigations, such as the characterization of nucleic acid structures or the screening of protein-ligand interactions. For the latter, an automated sample changer is also to be acquired as part of the measure, which should enable efficient screening of substance (fragment) e.g. for the development of a new class of antibiotics. The new in-cell NMR capabilities can be ideally combined with cryo-electron tomography. The planned combination of in-cell NMR and cryo-electron tomography will generate an outstanding added value for both foci of HHU, which is only available at a few locations worldwide.This measure is a new procurement that will serve to convert an already existing and fully intact 14.1 Tesla superconducting 600 MHz NMR magnet into a contemporary tool for in-cell and in-organoid NMR that is useful for the site.

该项目的主要目标是使氟原子（19F）的出色特性可用于HHU研究组的基于NMR的结构研究。因此，该措施代表了自2004年以来一直存在的生物分子NMR中心的必要应用扩展，并将能够对细胞系统以及更有效的抗生素发展产生高分辨率的见解。目前，HHU没有足够的可能性在生物大分子和生物系统中使用19F核旋转。但是，其他NMR中心的研究稳定增长，证实了19F核旋的广泛适用性和巨大的科学效用。 19F检测技术的真正好处源于以下事实：一方面，氟原子具有很好的NMR特性（NMR活性同位素的100％出现，高信号强度和NMR频率对化学环境的强依赖性）。此外，在生物系统（例如真核细胞）中仅以可忽略的数量存在19F。但是，有许多方法可以专门用19F标记分子。例如，这允许对其天然细胞环境的19F标记分子进行高度敏感和高分辨率的NMR研究，因为几乎没有电池中的背景信号。生物系统的常规NMR活性核并非如此（1H，13C，15N，31p）。因此，混凝土计划的19F-NMR应用包括研究神经肽的结构和动力学，G蛋白偶联受体以及使用所谓的内细胞内NMR方法的DNA介导的催化。此外，不仅使用孤立的细胞，而且首次使用所谓的三维器官，例如脑器官，例如脑器官。对于后者，自动样品更换器也将作为量度的一部分获取，该措施应有效筛选物质（片段），例如用于开发新的抗生素。新的内部NMR功能可以与冷冻电子层析成像结合使用。 The planned combination of in-cell NMR and cryo-electron tomography will generate an outstanding added value for both foci of HHU, which is only available at a few locations worldwide.This measure is a new procurement that will serve to convert an already existing and fully intact 14.1 Tesla superconducting 600 MHz NMR magnet into a contemporary tool for in-cell and in-organoid NMR that is useful for the 地点。