NMR STUDIES OF METABOLIC PATHWAYS IN VIVO AND IN VITRO

该建议的具体目标是：（1）发展高- 通过修改一个 现有的光谱仪成像和记录化学位移数据， 细胞核3 H和13 C;（2）研究细菌代谢， 真菌、植物和哺乳动物细胞;（3）通过使用 高场核磁共振，进入生物合成的机制， 维生素B12、青霉素和相关分子的作用方式 对健康和疾病至关重要;（4）使用 核磁共振实验的最高分辨率，以研究 在分子水平上的酶机制的动力学，使用 低温酶学 第一个长期目标是开发诊断和 分析NMR方法，将有一般的应用， 指纹正常和异常代谢谱， 生命系统，组织，灌注器官和血浆，第二 长远目标是发展核磁共振技术 技术，结合有机合成，酶学 和晶体结构的知识（如果可能），研究 在分子水平上的机制，以设计新的 基于机理的抑制剂，其结构将提供 用于设计用于治疗 细菌和寄生虫感染、肺气肿等。

The specific aims of this proposal are (1) to develop the high- resolution NMR spectroscopy of living systems by modifying an existing spectrometer to image and record chemical shift data for the nuclei 3H and 13C; (2) to study metabolism in bacterial, fungal, plant and mammalian cells; (3) to gain insight, via the use of high-field NMR, into the mechanism of the biosynthesis and mode of action of vitamin B12, penicillin and related molecules which are of vital importance in health and disease; and (4) to use the highest resolving power of the NMR experiment to study the dynamics of enzyme mechanism at the molecular level, using cryoenzymology. The first long-term objective is to develop diagnostic and analytical NMR methods which will have general application for fingerprinting both normal and aberrant metabolic profiles in living systems, tissue, perfused organs and plasma, The second long-term objective is concerned with the development of NMR techniques, in combination with organic syntheses, enzymology and knowledge of crystal structures (where possible), to study mechanism at the molecular level in order to devise new mechanism-based inhibitors whose structures will provide a lead for the design of novel drugs to be used in the treatment of bacterial and parasitic infections, emphysema, etc.