NMR STUDIES OF METABOLIC PATHWAYS IN VIVO AND IN VITRO

这项建议的具体目标是：(1)发展高技术含量的产品。 生物系统的分辨核磁共振波谱研究 现有的光谱仪用于成像和记录化学位移数据 ~3H和~(13)C核；(2)为了研究细菌的代谢， 真菌、植物和哺乳动物细胞；(3)通过使用 高场核磁共振，深入到生物合成和 维生素B12、青霉素及其相关分子的作用机制 对健康和疾病至关重要的；和(4)使用 最高分辨率的核磁共振实验研究 在分子水平上酶机制的动力学，使用 冷冻酶学。 第一个长期目标是开发诊断和 具有普遍应用前景的分析核磁共振方法 正常和异常代谢图谱的指纹图谱 生命系统、组织、灌流器官和血浆，第二种 核磁共振的发展是我们的长期目标 与有机合成、酶学相结合的技术 和晶体结构知识(在可能的情况下)，学习 在分子水平上的机制，以设计出新的 基于机理的抑制剂，其结构将提供先导 用于治疗的新药的设计 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.