Your mother was right, washing matters: An alkyne-analog of ibuprofen reveals unwanted reactivity of aromatic compounds with proteins during copper-catalyzed click chemistry.
Your mother was right, washing matters: An alkyne-analog of ibuprofen reveals unwanted reactivity of aromatic compounds with proteins during copper-catalyzed click chemistry.
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DOI：
10.1016/j.bmcl.2021.128260
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发表时间：
2021-09-15
影响因子：
2.7
通讯作者：
Pratt MR
中科院分区：
文献类型：
--
作者：
Cutolo G;Shankar SN;Pratt MR
生物正交化学，特别是铜（I）催化的叠氮化物-炔环加成（CuAAC），已经能够可靠地鉴定探针和药物的共价蛋白靶标。布洛芬是常用的止痛退烧药，以对映体外消旋体形式出售。有趣的是，立体异构体可以通过布洛芬-CoA硫酯中间体进行酶促转化，该中间体可能与蛋白质亲核试剂发生非特异性反应。在这里，我们使用布洛芬的炔烃类似物做出了两项发现。首先，我们发现布洛芬可能不会导致蛋白质显着的化学标记。然而，我们其次发现芳香族化合物可以在 CuAAC 反应过程中与蛋白质发生反应，除非它们被适当地从混合物中洗掉。假阳性标记的第二次发现对该方法的应用具有重要的技术意义。
Bioorthogonal chemistry, in particular the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), has enabled the robust identification of covalent protein targets of probes and drugs. Ibuprofen is commonly used pain and fever reducer and is sold as an enantiomeric racemate. Interestingly, the stereoisomers can be enzymatically converted through an ibuprofen-CoA thioester intermediate, which might non-specifically react with protein nucleophiles. Here, we use an alkyne-analog of ibuprofen to make two discoveries. First, we find that ibuprofen likely does not result in notable chemical labeling of proteins. However, we secondly find that aromatic compounds can react with proteins during the CuAAC reaction unless they are appropriately washed out of the mixture. This second discovery of false positive labeling has important technical implications for the application of this approach.
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影响因子：
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