Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, 3200008, Israel.
Angew Chem Int Ed Engl. 2017 Aug 28;56(36):10644-10655. doi: 10.1002/anie.201702370. Epub 2017 Aug 7.
The field of site-specific modification of proteins has drawn significant attention in recent years owing to its importance in various research areas such as the development of novel therapeutics and understanding the biochemical and cellular behaviors of proteins. The presence of a large number of reactive functional groups in the protein of interest and in the cellular environment renders modification at a specific site a highly challenging task. With the development of sophisticated chemical methodologies it is now possible to target a specific site of a protein with a desired modification, however, many challenges remain to be solved. In this context, transition metals in particular palladium-mediated C-C bond-forming and C-O bond-cleavage reactions gained great interest owing to the unique catalytic properties of palladium. Palladium chemistry is being explored for protein modifications in vitro, on the cell surface, and within the cell. Very recently, palladium complexes have been applied for the rapid deprotection of several widely utilized cysteine protecting groups as well as in the removal of solubilizing tags to facilitate chemical protein synthesis. This Minireview highlights these advances and how the accumulated knowledge of palladium chemistry for small molecules is being impressively transferred to synthesis and modification of chemical proteins.
近年来，由于其在新型治疗药物开发和理解蛋白质的生化和细胞行为等各个研究领域中的重要性，蛋白质的定点修饰领域引起了极大的关注。由于感兴趣的蛋白质和细胞环境中存在大量的反应性功能基团，因此在特定部位进行修饰是一项极具挑战性的任务。随着复杂化学方法的发展，现在可以用所需的修饰来靶向蛋白质的特定部位，然而，仍有许多挑战需要解决。在这种情况下，由于钯的独特催化特性，过渡金属特别是钯介导的 C-C 键形成和 C-O 键断裂反应引起了极大的兴趣。钯化学正在被探索用于体外、细胞表面和细胞内的蛋白质修饰。最近，钯配合物已被用于快速脱除几种广泛使用的半胱氨酸保护基团，并去除增溶标签，以促进化学蛋白质合成。这篇综述强调了这些进展，以及钯化学在小分子方面的积累知识如何令人印象深刻地被转移到化学蛋白质的合成和修饰上。
