Catalyst free hydrazone ligation for protein labeling and modification using electron-deficient benzaldehyde reagents
Catalyst free hydrazone ligation for protein labeling and modification using electron-deficient benzaldehyde reagents
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使用缺电子苯甲醛试剂进行蛋白质标记和修饰的无催化剂腙连接
DOI：
10.1039/c8ob01810c
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发表时间：
2018
影响因子：
3.2
通讯作者：
Shi Jing
中科院分区：
文献类型：
--
作者：
Xu Yang;Wang Yu;Liu Peiyuan;Chu Guo-Chao;Xu Huajian;Li Yi-Ming;Wang Jun;Shi Jing
生物正交反应已成为体外和体内位点特异性蛋白质标记和修饰的有价值的工具。腙和肟连接最近因其在生物分子缀合中的广泛应用而引起了相当大的关注。然而，这种反应在生理条件下动力学缓慢，并且由于催化剂而导致反应体系有毒或复杂化。在这项工作中，我们开发了一种缺电子苯甲醛试剂，它可以很容易地配备各种类型的生物功能分子，用于无催化剂的腙连接。该试剂不仅可以配备荧光染料或药物等小分子，还可以配备PEG等大分子。它们可以在中性 pH 值和室温下通过有效的腙反应精确连接到蛋白质的 C 末端。基于新试剂的无催化剂腙连接为蛋白质的位点特异性修饰提供了实用的方法。
Bioorthogonal reactions have emerged as valuable tools for site-specific protein labeling and modification in vitro and in vivo. Hydrazone and oxime ligation has recently attracted considerable attention for wide applications in the conjugation of biomolecules. However, this kind of reaction has suffered from slow kinetics under physiological conditions and toxicity or complications of the reaction system due to catalysts. In this work we have developed an electron-deficient benzaldehyde reagent, which can be easily equipped with various types of bio-functional molecules for catalyst-free hydrazone ligation. The reagent can be equipped with not only small molecules such as fluorescence dyes or drugs, but also macromolecules like PEG. These can be precisely ligated to the C-terminus of proteins by an efficient hydrazone reaction at neutral pH and room temperature. The new reagent based catalyst-free hydrazone ligation provides a practical approach for the site specific modification of proteins.