STRUCTURE ELUCIDATION OF CARCINOGEN-NUCLEOSIDE ADDUCTS

致癌物-核苷加合物的结构解析

• 批准号: 3941543
• 负责人: K B TOMER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3941543
• 关键词: DNA; biophysics; chemical carcinogen; chemical structure function; guanosine; hydroxylamine; mass spectrometry; molecular biology; nucleosides; physical chemical interaction; xanthine oxidase

One of the major research concerns at NIEHS is to understand the interactions between exogenous chemicals and biomolecules within the body. For a complete understanding of this interaction, the structures of the products of covalent interactions must be elucidated. Of special concern are the products of reactions between environmental carcinogens and DNA. As model systems, we are currently studying the in vitro interactions between 3-nitrofluorene and calf thymus DNA and between AZQ and quanosine. 3-Nitrofluorene must be reduced to the reactive hydroxylamine intermediate before it can react with DNA. This reductive interaction has been carried out in vitro using both chemical reduction and biologically mediated reduction (xanthine oxidase). The structure of the modified nucleoside isolated from the reaction has been elucidated by the use of a combination of FAB/MS and FAB/MS-MS and determine to be N- (deoxyguanosin- 8-yl)-3-aminofluoranthene. The analysis of the reaction of AZQ with quanosine has been initiated. An adduct has been isolated and tentatively identified. The final structure proof is currently in progress.

NIEHS的主要研究问题之一是了解