Department of Chemistry, School of Science, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8551, Japan.
J Am Chem Soc. 2023 Jul 5;145(26):14184-14189. doi: 10.1021/jacs.3c03394. Epub 2023 Jun 2.
The -nitrosation in selenoproteins such as glutathione peroxidase and thioredoxin reductase to produce -nitrososelenocysteines (Sec-SeNOs) has been proposed to play crucial roles in signaling processes mediated by reactive nitrogen species and nitrosative-stress responses, although chemical evidence for the formation of Sec-SeNOs has been elusive not only in proteins but also in small-molecule systems. Herein, we report the first synthesis of a Sec-SeNO by employing a selenocysteine model system that bears a protective molecular cradle. The Sec-SeNO was characterized using H and Se nuclear magnetic resonance as well as ultraviolet/visible spectroscopy and found to have persistent stability at room temperature in solution. The reaction processes involving the Sec-SeNO provide experimental information that serves as a chemical basis for elucidating the reaction mechanisms involving the SeNO species in biological functions, as well as in selenol-catalyzed NO generation from -nitrosothiols.
硒蛋白（如谷胱甘肽过氧化物酶和硫氧还蛋白还原酶）中的 -亚硝化作用会产生 -亚硝酰硒代半胱氨酸（Sec-SeNOs），这被认为在活性氮物种和硝化应激反应介导的信号转导过程中发挥关键作用，尽管不仅在蛋白质中，而且在小分子体系中，Sec-SeNOs 的形成的化学证据一直难以捉摸。在此，我们报告了首次通过采用带有保护分子摇篮的硒半胱氨酸模型系统来合成 Sec-SeNO。使用 H 和 Se 核磁共振以及紫外/可见光谱对 Sec-SeNO 进行了表征，并发现其在溶液中于室温下具有持久稳定性。Sec-SeNO 的反应过程提供了实验信息，为阐明涉及生物功能中 SeNO 物种的反应机制以及从 -亚硝基硫醇生成硒醇催化的 NO 提供了化学基础。
