Acyl azide modification of the ubiquitin C-terminus enables DUB capture,Chemical Communications

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Acyl azide modification of the ubiquitin C-terminus enables DUB capture
Chemical Communications ( IF 4.3 ) Pub Date : 2022-12-29 , DOI: 10.1039/d2cc06496k
Xiao Hua ₁ , Yanyan Guo ₁ , Yu Wang ₁ , Guo-Chao Chu ₂ , Pincheng Li ₃ , Jing Shi ₁

Affiliation

Deubiquitinating enzyme (DUB) abnormalities are associated with many diseases. Previous attempts have been made to introduce various chemical groups such as alkynes, unsaturated olefins and alkyl halides to the C-terminus of ubiquitin (Ub) to capture the active-site cysteine residue in DUBs for structural and biochemical studies. Here, we find that a Ub C-terminal acyl azide can capture DUBs, thereby forming thioester bonds in buffers and cell lysates. This finding not only makes ubiquitin acyl azide a chemical probe for capturing DUBs, but also extends the utility of azide groups in biological applications.

中文翻译：

泛素 C 端的酰基叠氮化物修饰使 DUB 捕获成为可能

去泛素化酶 (DUB) 异常与许多疾病有关。先前已尝试将各种化学基团（如炔烃、不饱和烯烃和卤代烷）引入泛素 (Ub) 的 C 末端，以捕获 DUB 中的活性位点半胱氨酸残基，用于结构和生化研究。在这里，我们发现 Ub C 端酰基叠氮化物可以捕获 DUB，从而在缓冲液和细胞裂解物中形成硫酯键。这一发现不仅使泛素酰基叠氮化物成为捕获 DUB 的化学探针，而且扩展了叠氮基团在生物学应用中的效用。

更新日期：2022-12-29

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