A National Instrumentation Facility for NMR of Biological Solids

该提案要求为建立生物固体核磁共振国家仪器设施提供资金。新的固体核磁共振技术将被开发和应用于解决生物科学中的实际和重要问题。该设施将由三个现有的固体光谱仪组成，另外两个将在未来两年内建造。通过合作研究，将开发或改进的新固体核磁共振实验包括：13C-170双交叉极化、旋转回波双共振和但丁标记的13C-13C自旋扩散。这些实验将与现有的固体核磁共振技术相结合，以鉴定昆虫外骨骼和植物细胞壁中的交联物，建立药物对细菌细胞壁新陈代谢的作用机制，鉴定固定化酶中的结合部位，测量酶活性部位内的动力学和构象灵活性，测量脂链中多个位置在凝胶状态下的流动性，而无需特定的脂类标记，并非交叉地监测药物、除草剂和杀虫剂在哺乳动物组织中的分解代谢。首席研究员有着长期成功的生物合作历史，他的实验室展示了开发新核磁共振技术的能力，他积累了具有其他任何实验室无法比拟的能力的固体核磁共振光谱仪，首席研究员在将基础科学研究成果转化为有用的最终产品方面拥有经验。出于这些原因，建议提供支持。

This proposal requests funds to establish a National Instrumentation Facility for NMR of Biological Solids. New solids NMR techniques will be developed and applied to solve practical and important problems in the biological sciences. The Facility will consist of three existing solids spectrometers, with two more to be built over the next two years. Via collaborative research, new solids NMR experiments to be developed or refined include: 13C-170 double-cross polarization, rotational-echo double resonance, and DANTE-labeled 13C-13C spin diffusion. These experiments will be combined with existing solids NMR techniques to identify cross-links in insect exoskeleton and plant cell walls, to establish the mechanism of drug action on bacterial cell-wall metabolism, to identify binding sites in immobilized enzymes, to measure the dynamics and conformational flexibility within the active sites of enzymes, to measure the mobility of multiple sites in lipid chains in the gel state without specific labeling of the lipids, and to monitor nondescructively the catabolism of drugs, herbicides, and pesticides in mammalian tissue. The principal investigator has a long history of successful biological collaborations, his laboratory has demonstrated an ability to develop new NMR technology, he has accumulated solids NMR spectrometers with capabilities unmatched by any other single laboratory, and the principal investigator has experience in translating results of basic scientific research into useful end products. For these reasons support is recommended.