A target identification platform derived from the bioorthogonal activation of reactive species is described. We explore the reactivity of halogenated enamine N-oxides and report that the previously undisclosed α,γ-halogenated enamine N-oxides can be reduced biooorthogonally by diboron reagents to produce highly electrophilic α,β-unsaturated haloiminium ions suitable for labeling a range of amino acid residues on proteins in a 1,2- or 1,4-fashion. Affinity labeling reagents bearing this motif enable ligand-directed protein modification and afford highly sensitive and selective target identification in unbiased chemoproteomics experiments. Target identification is supported in both cell lysate and live cells.

描述了源自活性物质的生物正交激活的目标识别平台。我们探索了卤代烯胺N-氧化物的反应性，并报道了先前未公开的 α,γ-卤代烯胺N-氧化物可以通过二硼试剂生物正交还原，产生高度亲电子的 α,β-不饱和卤代亚胺离子，适合标记一系列氨基蛋白质上的酸残基以 1,2- 或 1,4- 形式存在。带有该基序的亲和标记试剂能够实现配体定向的蛋白质修饰，并在无偏化学蛋白质组学实验中提供高度灵敏和选择性的靶标识别。细胞裂解物和活细胞均支持靶标识别。