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（19 F）的优异性能可用于HHU研究小组的NMR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中心的重要应用扩展，并将实现对细胞系统的高分辨率洞察以及更有效的抗生素开发。目前，HHU还没有足够的可能性在生物大分子和生命系统中使用19 F核自旋。然而，来自其他NMR中心的稳步增长的研究证实了19 F核自旋的广泛适用性和巨大的科学用途。19 F检测技术的真实的益处源于这样的事实，即一方面，氟原子具有非常好的NMR性质（100%出现NMR活性同位素、高信号强度和NMR频率对化学环境的强依赖性）。此外，19 F仅以可忽略的量存在于生物系统中，例如真核细胞。然而，有许多方法可以用19 F特异性标记分子。例如，这允许对天然细胞环境的19 F标记分子进行高灵敏度和高分辨率的NMR研究，因为实际上没有背景信号从细胞发出。对于生物系统的常规NMR活性核（1H，13 C，15 N，31 P），情况并非如此。因此，具体计划的19 F-NMR应用包括使用所谓的细胞内NMR方法研究神经肽、G蛋白偶联受体和DNA介导的催化的结构和动力学。此外，细胞内核磁共振将进一步发展，不仅使用分离的细胞，而且首次使用所谓的三维类器官，如脑类器官。除了细胞内核磁共振，19 F核磁共振光谱还为体外研究提供了独特的可能性，如核酸结构的表征或蛋白质-配体相互作用的筛选。对于后者，作为措施的一部分，还将获得一个自动样品更换器，这将能够有效地筛选物质（碎片），例如用于开发一类新的抗生素。新的细胞内NMR功能可以理想地与低温电子断层扫描相结合。计划中的细胞内NMR和低温电子断层扫描的组合将为HHU的两个焦点产生出色的附加值，这在全球范围内仅在少数几个地点可用。这项措施是一项新的采购，将有助于将现有的和完全完整的14.1特斯拉超导600 MHz NMR磁体转换为对该网站有用的细胞内和无机NMR的当代工具。