Selective Triazenation Reaction (STaR) of Secondary Amines for Tagging Monomethyl Lysine Post‐Translational Modifications
Selective Triazenation Reaction (STaR) of Secondary Amines for Tagging Monomethyl Lysine Post‐Translational Modifications
复制标题
用于标记单甲基赖氨酸翻译后修饰的仲胺选择性三嗪化反应 (STaR)
DOI：
10.1002/ange.202013997
复制
发表时间：
2021
影响因子：
--
通讯作者：
Raj, Monika
中科院分区：
文献类型：
--
作者：
Nwajiobi, Ogonna;Mahesh, Sriram;Streety, Xavier;Raj, Monika
赖氨酸单甲基化(KME)是一种有效的翻译后修饰(PTM)，负责调节生物过程并与疾病有关，因此在全球范围内识别这些甲基化标记受到了极大的关注。然而，这方面的进展一直是具有挑战性的，因为在赖氨酸上添加一个小的甲基导致体积、电荷和疏水性的变化可以忽略不计。在这里，我们报告了一种增强化学技术的选择性三氮化反应，我们称之为“STAR”，使用芳烃重氮盐来实现从生物相容条件下的复杂混合物中高选择性、快速和健壮地标记KME多肽。尽管得到的三氮烯与KME的连接是稳定的，但我们强调了三氮烯共轭化合物的有效解偶联，以便在需要的温和条件下提供未经修饰的起始组分。我们的工作建立了一种独特的化学选择性、无痕迹生物结合策略，用于选择性浓缩KME PTMS。
Lysine monomethylation (Kme) is an impactful post‐translational modification (PTM) responsible for regulating biological processes and implicated in diseases, thus there is great interest in identifying these methylation marks globally. However, the progress in this area has been challenging because the addition of a small methyl group on lysine leads to negligible change in the bulk, charge, and hydrophobicity. Herein, we report an empowering chemical technology selective triazenation reaction, which we term “STaR”, of secondary amines using arene diazonium salts to achieve highly selective, rapid, and robust tagging of Kme peptides from a complex mixture under biocompatible conditions. Although the resulting triazene‐linkage with Kme is stable, we highlight the efficient decoupling of the triazene‐conjugate to afford unmodified starting components under mild conditions when desired. Our work establishes a unique chemoselective, traceless bioconjugation strategy for the selective enrichment of Kme PTMs.