Development of Fluorine Nuclear Magnetic Resonance (NMR) Spectroscopy as a Versatile Probe of Structure and Chemical Environment in Proteins

开发氟核磁共振 (NMR) 光谱作为蛋白质结构和化学环境的多功能探针

• 批准号: 1708773
• 负责人: Angela Gronenborn
• 金额: $ 70万
• 依托单位: University of Pittsburgh
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1708773&HistoricalAwards=false
• 关键词: Development; Fluorine; Nuclear; Magnetic; Resonance; Development; Fluorine; Nuclear; Magnetic; Resonance

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Professors Angela M. Gronenborn from the University of Pittsburgh and Tatyana Polenova of the University of Delaware. The research project involves the use of fluorine nuclear magnetic spectroscopy (NMR), a versatile analytical tool in chemistry used for probing chemical structures and geometries. Naturally-occurring, magnetically-active isotopes of elements such as deuterium (a form of hydrogen), carbon (C-13) and nitrogen(N-15) are most commonly studied in biomolecular NMR; however, fluorine (F-19) is a very attractive and sensitive nucleus, which offers rich information about molecules in the solution and solid states. The overall goal of this research program is to establish fluorine-19 NMR spectroscopy as a versatile approach for describing the structure and geometry of proteins. The project involves an integration of computational and experimental approaches. The broader impact plans integrate scientific training with studies in the humanities in an effort to prepare students for communicating science to the public. In addition, there are educational activities that involve a graduate student exchange program between the laboratories of the academic researchers and industry collaborators at Bruker. These students spend 2-3 weeks acquiring complementary training in advanced experimental biophysical chemistry, hands-on NMR spectroscopy, and instrumentation. Outreach activities for undergraduates and high-school students attract students with diverse backgrounds into the science, technology, engineering and mathematics (STEM) disciplines. The specific objectives of this project are to develop fluorine-19 chemical shifts as a probe of geometry, electronic structure, chemical reactivity, and dynamics in peptides and proteins. The project integrates fluorine-19 solution and solid-state NMR parameters with quantum chemical calculations. The research exploits the vast range of chemical shifts and the sparsity of fluorine-19 sites, to develop solution and solid-state NMR experiments for mapping out long-range distances and interaction sites in peptides and proteins. The research may overcome the current challenges in the calculations of accurate fluorine-19 chemical shift tensors for biochemical systems and in fluorine-based distance measurements. Given the simplicity of biosynthetic incorporation of fluorine into a wide variety of specific and unique sites, the approaches enable fluorine-19 solution and solid-state NMR applications for a broad range of biochemical systems.

有了这个奖项，化学部门的化学过程计划是匹兹堡大学的Angela M. Gronenborn教授和特拉华大学的Tatyana Polenova资助。该研究项目涉及使用氟核磁光谱（NMR），这是一种用于探测化学结构和几何形状的化学中的多功能分析工具。在生物分子NMR中，最常研究诸如氘（氢），碳（C-13）和氮（N-15）等元素的自然磁性同位素；但是，氟（F-19）是一个非常有吸引力和敏感的核，它提供了有关溶液和固态分子的丰富信息。该研究计划的总体目标是建立氟-19 NMR光谱，作为描述蛋白质结构和几何形状的多功能方法。该项目涉及计算和实验方法的整合。更广泛的影响计划将科学培训与人文学科的研究结合起来，以便为学生提供向公众传达科学的准备。此外，还有一些教育活动涉及学术研究人员和布鲁克的行业合作者之间的研究生交流计划。这些学生花了2-3周的时间在高级实验生物物理化学，动手NMR光谱和仪器中获得互补培训。针对本科生和高中生的外展活动吸引了具有不同背景的学生进入科学，技术，工程和数学（STEM）学科。该项目的具体目标是开发氟-19的化学位移，作为肽和蛋白质中的几何结构，化学反应性以及动力学的探针。该项目将氟-19溶液和固态NMR参数与量子化学计算相结合。该研究利用了氟-19个位点的广泛化学位移和稀疏性，以开发溶液和固态NMR实验，以绘制肽和蛋白质中的长距离距离和相互作用位点。这项研究可能会在精确的氟-19化学移位张量和基于氟的距离测量中的准确氟-11化学位移张量计算中克服当前的挑战。鉴于将氟的生物合成掺入到各种特定和独特的地点中的简单性，该方法可实现氟-19溶液和固态NMR应用，用于广泛的生化系统。