Light-Controlled Tyrosine Nitration of Proteins
Light-Controlled Tyrosine Nitration of Proteins
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DOI：
10.1002/anie.202102287
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发表时间：
2021-05-10
影响因子：
16.6
通讯作者：
Wang, Huan
中科院分区：
文献类型：
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作者：
Long, Tengfang;Liu, Lei;Wang, Huan
蛋白质的酪氨酸硝化是体内最重要的翻译后氧化修饰之一。缺乏高效、化学选择性的蛋白质酪氨酸硝化试剂是其生理生化研究的主要障碍。在此，我们报告了一种可推广的策略，采用生物相容性二硝基咪唑试剂的光控蛋白酪氨酸硝化。在390 nm照射下，二硝基咪唑在中性水性缓冲液条件下以快速动力学和高化学选择性有效地将肽和蛋白质中的酪氨酸残基转化为3-硝基酪氨酸残基。3-硝基酪氨酸残基的掺入增强了套索肽天然产物的热稳定性，并赋予小鼠肿瘤坏死因子-α强免疫原性以打破自身耐受。该方法的光控时间分辨率允许研究酪氨酸硝化对α-突触核蛋白自组装行为的影响。
Tyrosine nitration of proteins is one of the most important oxidative post-translational modifications in vivo. A major obstacle for its biochemical and physiological studies is the lack of efficient and chemoselective protein tyrosine nitration reagents. Herein, we report a generalizable strategy for light-controlled protein tyrosine nitration by employing biocompatible dinitroimidazole reagents. Upon 390 nm irradiation, dinitroimidazoles efficiently convert tyrosine residues into 3-nitrotyrosine residues in peptides and proteins with fast kinetics and high chemoselectivity under neutral aqueous buffer conditions. The incorporation of 3-nitrotyrosine residues enhances the thermostability of lasso peptide natural products and endows murine tumor necrosis factor-alpha with strong immunogenicity to break self-tolerance. The light-controlled time resolution of this method allows the investigation of the impact of tyrosine nitration on the self-assembly behavior of alpha-synuclein.