NMR Studies of Phoshate Metabolism in Protozoan Parasite

描述(申请人提供)：本研究的目的是使用HIGH 现场核磁共振波谱在代谢研究中的应用 在克氏锥虫中发生的过程并利用这些信息来帮助 发现新的药物靶点。下一步将采用的方法 研究T ruzi的代谢过程涉及到使用600和 750 MHz溶液和固体核磁共振研究~(31)P和~(13)C谱 上鞭毛体和无鞭毛体都有。到目前为止，初步的31P和13C核磁共振 已经获得了光谱，但碳水化合物和 磷酸盐代谢，氨基酸和磷酸盐代谢，还没有 调查过了。因此，下一步需要做的是使第一个 碳和磷代谢之间的相关性，做功似乎是 由于发现了大量的焦磷酸盐，这是必不可少的。也就是说， 焦磷酸盐的作用需要澄清。在这里，监控两者的能力 可溶的缩合磷酸盐(使用溶液核磁共振)以及不溶的 磷酸盐(使用固态魔角样品旋转技术)应 事实证明这是无价之宝。此外，将使用溶液和固态核磁共振技术来 调查在T ruzi中发现的不寻常的多a-羟基辛酸酯物种，它 通过与中发现的聚磷酸盐/聚-CX-羟基丁酸酯物种类比 原核生物可能代表着酸性钙体中的原始离子通道。

DESCRIPTION (provided by applicant): The aim of this research is to use high field nuclear magnetic resonance spectroscopy to investigate the metabolic processes that occur in Trypanosoma cruzi and to use this information to help discover new drug targets. The methods to be employed for the further investigation of the metabolic processes in T cruzi involve the use of 600 and 750 MHz solution and solid-state NMR to study the 31P and 13C NMR spectroscopy of both epimastigote and amastigote forms. To date, initial 31P and 13C NMR spectra have been obtained, but the relationships between carbohydrate and phosphate metabolism, and amino acid and phosphate metabolism, have not been investigated. What needs to be done next, therefore, is to make the first correlations between carbon and phosphate metabolism, work that appears to be essential due to the very large levels of pyrophosphate found. That is, the role of pyrophosphate needs to be clarified. Here, the ability to monitor both soluble condensed phosphates (using solution NMR) as well as insoluble phosphates (using solid-state magic-angle sample-spinning techniques) should prove invaluable. Plus, solution and solid-state NMR techniques will be used to investigate the unusual poly-a-hydroxyoctanoate species found in T cruzi, which by analogy with the polyphosphate/poly-cx-hydroxybutyrate species found in prokaryotes may represent a primitive ion channel in the acidocalcisome.