Acquisition of a 900 MHz NMR Spectrometer

购买 900 MHz NMR 波谱仪

• 批准号: 6548308
• 负责人: ROBERT Guy GRIFFIN
• 金额: $ 531.13万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6548308
• 关键词: biomedical equipment purchase; health science research; nuclear magnetic resonance spectroscopy; structural biology

DESCRIPTION: We propose to purchase a 900 MHz NMR spectrometer and operate it as a national user facility. The scientific experiments planned involve solution NMR and high-resolution solid state NMR. Solution NMR: the solution experiments are directed at structural problems that: are at or beyond the capabilities of presently available instrumentation. We emphasize the importance of sample preparation technologies that enable us to study the most significant biological problems rather than just well behaved model systems. Thus, most of our molecule also represent targets for development of drugs against cancer, viral infection, bacterial and immune diseases Our novel protein expression strategies have allowed us to overcome most of the problems of poor solubility and stability for nearly all projects we are working on so that the limiting hurdle of solution structure determination is shifting back from sample preparation to spectral resolution and sensitivity. Our solution NMR studies will include structures of large protein-protein and protein-nucleic acid complexes, and structures of member C proteins. The high-field spectrometer will also be utilized, to characterize protein-ligand complexes in the sear h for agents against cancer, viral infection and as immuno-suppressants. We will pursue larger structures with R and crystallography to benefit from the synergy of both techniques. Solid State NMR: S lid-state experiments will utilize a new class of dipolar recoupling techniques that have produced the initial de novo structure of a small molecule. We will extend these techniques to microcrystalline proteins. Further, the methods will permits us to address questions of the mechanism of H+ pumping in bacteriorhodopsin and to develop methods to perform structural studies of membrane proteins. The de novo structure of gas vesicles will emerge from these investigations. A second area of interest is the structure of amyloid fibrils where e plan to determine the structure of the A protein associated with Alzheimer's disease, as well as a fibril forming SH-3 domain and a-synuclein associated with Parkinson's disease. Finally, high fields will permit us to develop 17 O NMR as an important new tool for studies of biological systems.

描述：我们建议购买一台900 MHz NMR光谱仪，并将其作为国家用户设施运营。计划的科学实验包括溶液NMR和高分辨率固态NMR。 溶液NMR：解决方案实验针对的是结构问题，这些结构问题处于或超出了目前可用仪器的能力。我们强调样品制备技术的重要性，使我们能够研究最重要的生物学问题，而不仅仅是行为良好的模型系统。因此，我们的大多数分子也代表了开发抗癌药物的目标，病毒感染，细菌和免疫疾病我们的新型蛋白质表达策略使我们能够克服我们正在研究的几乎所有项目的溶解度和稳定性差的问题，因此溶液结构测定的限制性障碍从样品制备转移到光谱分辨率和灵敏度。我们的溶液NMR研究将包括大蛋白质-蛋白质和蛋白质-核酸复合物的结构，以及成员C蛋白质的结构。高场光谱仪也将被用来表征蛋白质-配体复合物，用于抗癌剂、病毒感染剂和免疫抑制剂。我们将寻求更大的结构， R和晶体学从这两种技术的协同作用中受益。 固态NMR：盖态实验将利用一类新的偶极再偶联技术，这种技术已经产生了小分子的初始从头结构。我们将把这些技术扩展到微晶蛋白质。此外，该方法将使我们能够解决H+泵在细菌视紫红质的机制问题，并开发方法来进行膜蛋白的结构研究。从这些研究中将出现气体囊泡的从头结构。第二个感兴趣的领域是淀粉样蛋白原纤维的结构，其中我们计划确定与阿尔茨海默病相关的A蛋白的结构，以及与帕金森病相关的原纤维形成SH-3结构域和α-突触核蛋白。最后，高领域将使我们能够开发17 O NMR作为一个重要的新工具，用于生物系统的研究。