Site-selective chemical modification of protein side chain has probed enormous opportunities in the fundamental understanding of cellular biology and therapeutic applications. Primarily, in the field of biopharmaceuticals, the formulation of bioconjugates has been found to have more potential than an individual constituent. In this regard, Lysine and Cysteine are the most widely used endogenous amino acid for these purposes. Recently, the aromatic side chain residues (Trp, Tyr, and His) that are low abundant in protein have gained more attention in therapeutic applications due to their advantages of chemical reactivity and specificity. This review discusses the site-selective bioconjugation methods for aromatic side chains (Trp, Tyr and His) and highlights the developed strategies in the last three years, along with their applications. Also, the review highlights the prevalent methods published earlier. We have examined that metal-catalyzed and photocatalytic reactions are gaining more attention for bioconjugation, though their practical operation is under development. The review has been summarized with the future perspective of protein and peptide conjugations contemplating therapeutic applications and challenges.

蛋白质侧链的位点选择性化学修饰为细胞生物学和治疗应用的基本理解提供了巨大的机会。首先，在生物制药领域，已发现生物偶联物的配方比单个成分具有更大的潜力。在这方面，赖氨酸和半胱氨酸是用于这些目的的最广泛使用的内源性氨基酸。最近，蛋白质中低丰度的芳香侧链残基（Trp、Tyr 和 His）由于其化学反应性和特异性的优势而在治疗应用中受到更多关注。本综述讨论了芳香侧链（Trp、Tyr 和 His）的位点选择性生物偶联方法，并重点介绍了过去三年中开发的策略及其应用。还，该评论重点介绍了较早发表的流行方法。我们已经研究了金属催化和光催化反应在生物共轭方面越来越受到关注，尽管它们的实际操作正在开发中。该综述总结了蛋白质和肽缀合的未来前景，考虑了治疗应用和挑战。