Hydrolytic Cleavage of RNA by Metal Complexes; A Fundamental Study in Catalysis

9318581巴什金华盛顿大学-圣路易斯华盛顿大学化学系的詹姆斯·K·巴什金博士获得了无机化学、生物无机化学和金属有机化学项目的支持，以研究金属催化的核糖核酸的水解性切割。为了探索这些反应的机制，我们将使用已知的配位几何结构的金属络合物来研究RNA的水解和切割。可能的作用模式，包括路易斯酸催化，亲核或碱催化，以及内外球金属与底物的相互作用，将被探索。这些机制信息将被进一步用于设计一系列人工合成的核酶，这些核酶将模仿天然核酶切割特定RNA序列的能力。为了获得快速的动力学数据，将开发几种新的RNA裂解分析方法。DNA和RNA中遗传密码的构建和分解涉及对活细胞至关重要的化学过程，但这些过程的许多方面却知之甚少。这项研究的目的是确定DNA和RNA代码被分解的化学机制。这些化学发现可能被应用于破坏由突变或感染引起的不受欢迎的遗传密码。

9318581 Bashkin Washington Univ - St. Louis Dr. James K. Bashkin, Chemistry Department, Washington University, is supported in the Inorganic, Bioinorganic, and Organometallic Chemistry Program, for investigations of the metal-catalyzed hydrolytic cleavage of RNA. To probe the mechanisms of these reactions, RNA hydrolysis and cleavage will be studied using metal complexes with known coordination geometries. Possible modes of action, including Lewis acid catalysis, nucleophilic or base catalysis, and inner- and outer-sphere metal-substrate interactions, will be probed. The mechanistic information will be further utilized to design a series of synthetic ribozymes which will mimic the ability of natural ribozymes to cleave specific RNA sequences. In order to obtain rapid kinetic data, several new RNA cleavage assays will be developed. The construction and breakdown of the genetic code in DNA and RNA involves chemical processes that are of fundamental importance to living cells, yet many aspects of these processes are poorly understood. The goal of this research is to determine the chemistry by which DNA and RNA codes are disassembled. These chemical discoveries may be applied to the destruction of undesirable genetic codes which arise from mutation or infection.