Site‐selective chemical modifications of proteins have emerged as a potent technology in chemical biology, materials science, and medicine, facilitating precise manipulation of proteins with tailored functionalities for basic biology research and developing innovative therapeutics. Compared to traditional recombinant expression methods, one of the prominent advantages of chemical protein modification lies in its capacity to decorate proteins with a wide range of functional moieties, including non‐genetically encoded ones, enabling the generation of novel protein conjugates with enhanced or previously unexplored properties. Among these, approaches for dual or multiple protein modifications are increasingly garnering attention, as it has been found that single modifications of proteins are inadequate to meet current demands. Therefore, in light of the rapid developments in this field, this review provides a timely and comprehensive overview of the latest advancements in chemical and biological approaches for protein dual functionalization. It further discusses their advantages, limitations, and potential future directions in this relatively nascent area.

中文翻译：

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蛋白质化学选择性双重修饰的最新工具箱


蛋白质的位点选择性化学修饰已成为化学生物学、材料科学和医学领域的一项强大技术，有助于通过定制功能对蛋白质进行精确操作，用于基础生物学研究和开发创新疗法。与传统的重组表达方法相比，化学蛋白质修饰的显着优势之一在于其能够用多种功能部分（包括非基因编码的部分）修饰蛋白质，从而能够生成具有增强或以前未开发过的新型蛋白质缀合物。特性。其中，双重或多重蛋白质修饰的方法越来越受到关注，因为已经发现蛋白质的单一修饰不足以满足当前的需求。因此，鉴于该领域的快速发展，本文及时、全面地概述了蛋白质双功能化的化学和生物学方法的最新进展。它进一步讨论了它们在这个相对新兴领域的优势、局限性和潜在的未来方向。