Glutathione Mediates Control of Dual Differential Bio-orthogonal Labelling of Biomolecules
Glutathione Mediates Control of Dual Differential Bio-orthogonal Labelling of Biomolecules
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DOI：
10.1002/anie.202313063
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发表时间：
2023-11-13
影响因子：
16.6
通讯作者：
Burley，Glenn A.
中科院分区：
文献类型：
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作者：
Peschke，Frederik;Taladriz-Sender，Andrea;Burley，Glenn A.
传统的生物正交反应发现方法侧重于开发试剂对，这些试剂对相互反应的速度比它们的代谢降解速度快。谷胱甘肽（GSH）通常负责大多数生物正交试剂的失活。在这里，我们证明了谷胱甘肽促进了Cu催化的（3+2）环加成反应在动力胺和叠氮化物之间。我们发现谷胱甘肽作为氧化还原调节剂来控制这些环加物中的Cu氧化态。该反应的速率增强是针对动力学底物的，并且可以通过Cu:GSH的比例来调节。这种独特的GSH介导的反应性梯度随后通过两种不同的化学选择性（3+2）环加成用于多肽和寡核苷酸的双顺序生物正交标记。
Traditional approaches to bio‐orthogonal reaction discovery have focused on developing reagent pairs that react with each other faster than they are metabolically degraded. Glutathione (GSH) is typically responsible for the deactivation of most bio‐orthogonal reagents. Here we demonstrate that GSH promotes a Cu‐catalysed (3+2) cycloaddition reaction between an ynamine and an azide. We show that GSH acts as a redox modulator to control the Cu oxidation state in these cycloadditions. Rate enhancement of this reaction is specific for ynamine substrates and is tuneable by the Cu:GSH ratio. This unique GSH‐mediated reactivity gradient is then utilised in the dual sequential bio‐orthogonal labelling of peptides and oligonucleotides via two distinct chemoselective (3+2) cycloadditions.