MECHANISTIC STUDIES OF PEROXYNITRITE BIOCHEMISTRY

过氧亚硝酸盐生物化学机理研究

• 批准号: 2193242
• 负责人: Scott S Bohle
• 金额: $ 19.79万
• 依托单位: UNIVERSITY OF WYOMING
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 1998-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2193242
• 关键词: antioxidants; chemical reaction; chemical synthesis; endopeptidases; enzyme mechanism; gene mutation; heavy metals; intermolecular interaction; method development; mutagens; nitrites; nitrogen oxides; phospholipids; protease inhibitor

DESCRIPTION: This is a proposal to develop methods to synthesize stable peroxynitrite salts in pure form and to study the fundamental chemistry of peroxynitrite and its reactions with biological molecules. Peroxynitrite is a highly reactive reaction product of nitric oxide and superoxide that is thought to mediate biological oxidative damage where these precursors are formed together. Mechanistic studies of peroxynitrite chemistry have been hindered by the difficulty of obtaining peroxynitrite of high purity. This proposal builds upon Dr. Bohle's recent success in synthesizing tetramethylammonium peroxynitrite in pure crystalline form. Dr. Bohle proposes 1) work to optimize the synthetic method and to adapt it for synthesizing heavy metal peroxynitrite salts; 2) spectroscopic characterization of the salts and studies of peroxynitrite decomposition mechanisms in solution; 3) studies of the reaction of peroxynitrite with phospholipids; 4) mechanistic studies of the inactivation of sulfhydryl proteases by nitrogen oxides and peroxynitrite; 5) identification of potential markers products for peroxynitrite reactions with antioxidants; and 6) identification of products of nucleic acid modification by peroxynitrite.

描述：这是一项关于开发合成方法的建议 纯态稳定的过氧亚硝酸盐及其基本性质的研究 过氧亚硝酸盐的化学及其与生物分子的反应。 过氧亚硝酸盐是一氧化氮和亚硝酸根的高度反应产物 被认为介导生物氧化损伤的超氧化物 这些前驱物质是一起形成的。机械结构的研究 过氧亚硝酸根化学一直受到困难的阻碍 获得高纯度的过氧亚硝酸根。这项建议是建立在Dr。 Bohle最近成功地合成了过氧亚硝酸四甲铵 以纯水晶的形式存在。Bohle博士建议1)努力优化 一种合成方法及其在重金属合成中的应用 过氧亚硝酸盐；2)盐的光谱表征和 溶液中过亚硝酸根分解机理的研究 过氧亚硝酸根与磷脂反应的研究 黄曲霉毒素对水解酶失活机理的研究 氮氧化物和过亚硝酸根；5)潜在标记的鉴定 过氧亚硝酸根与抗氧化剂反应的产物； 过氧亚硝酸核酸修饰产物的鉴定。