MECHANISTIC STUDIES OF PEROXYNITRITE BIOCHEMISTRY

过氧亚硝酸盐生物化学机理研究

• 批准号: 2546026
• 负责人: Scott S Bohle
• 金额: $ 13.91万
• 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 1999-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2546026
• 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：这是一项开发合成方法的提案 稳定的过氧亚硝酸盐在纯形式和研究的基本 过氧亚硝酸盐化学及其与生物分子的反应。 过氧亚硝酸盐是一氧化氮的高活性反应产物， 超氧化物，被认为是介导生物氧化损伤， 这些前体一起形成。 机制研究 过氧亚硝酸盐化学已经受到以下困难的阻碍： 得到高纯度的过氧亚硝酸盐。这一建议建立在博士。 Bohle最近成功合成过亚硝酸四甲基铵 以纯晶体的形式。博勒博士建议：1）努力优化 合成方法和使其适用于合成重金属 过氧亚硝酸盐; 2）盐的光谱表征， 过氧亚硝酸根在溶液中分解机理的研究; 3） 过氧亚硝酸盐与磷脂反应的研究; 4） 巯基蛋白酶失活机理的研究 氮氧化物和过氧亚硝酸盐; 5）潜在标志物的鉴定 用于过氧亚硝酸盐与抗氧化剂反应的产物;以及6） 过氧亚硝酸根核酸修饰产物的鉴定。

项目成果

Cyclohexadienone diazeniumdiolates from nitric oxide addition to phenolates.

由一氧化氮加成酚盐生成环己二烯酮二氮烯鎓二醇。

• DOI: 10.1021/jo000513o
• 发表时间: 2000
• 期刊: The Journal of organic chemistry
• 作者: Bohle,DS;Imonigie,JA
• 通讯作者: Imonigie,JA

O-atom scrambling in the aqueous isomerization of pernitrous acid.

过亚硝酸水溶液异构化中的 O 原子扰乱。

• DOI: 10.1006/niox.1997.0155
• 发表时间: 1997
• 期刊: Nitric oxide : biology and chemistry
• 作者: Bohle,DS;Hansert,B
• 通讯作者: Hansert,B

Isolation and oxygenation reactions of nitrosylmyoglobins.

亚硝酰肌红蛋白的分离和氧化反应。

• DOI: 10.1016/s0076-6879(96)69008-9
• 发表时间: 1996
• 期刊: Methods in enzymology
• 作者: Arnold,EV;Bohle,DS
• 通讯作者: Bohle,DS

Radical dinitroalkane dianions from the nitration of nitroalkanes by peroxynitrite.

• DOI: 10.1021/tx0001474
• 发表时间: 2000-09
• 期刊: Chemical research in toxicology
• 影响因子: 4.1
• 作者: E. V. Arnold;D. Bohle;Y. Hu