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.
