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

James K. Bashkin博士，华盛顿大学化学系，从事无机、生物无机和有机金属化学项目，研究金属催化的RNA水解裂解。为了探索这些反应的机制，RNA水解和切割将使用金属配合物与已知的配位几何研究。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-底物相互作用，将被探讨。这些机制信息将被进一步用于设计一系列的合成核酶，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，一些新的RNA裂解实验将被开发出来。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尚不清楚。这项研究的目的是确定DNA和RNA密码被分解的化学过程。这些化学发现可用于破坏由突变或感染引起的不良遗传密码。

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.