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生物正交反应在化学生物学的研究中发挥着越来越重要的作用.传统的生物正交反应以新化学键生成的连接反应为主,其在实现生物分子的“标记”、“示踪”和“捕捉”等研究中发挥着重要作用.近年来,一类新兴的反应类型——以化学键断裂为基础的生物正交剪切反应逐渐发展起来,并在分子的“释放”、“激活”和“操控”等方面得到了越来越广泛的应用.本文首先重点介绍了生物正交剪切反应,总结了这些反应的特点、适用范围和已经实现的用途.随后通过具体的例子介绍了这些反应在化学生物学中的应用,包括小分子前药的激活、蛋白质功能的调控、细胞的工程化等.最后文章对生物正交剪切反应的发展趋势进行了展望.“,”Bioorthogonal reactions enable us to study and manipulate biological processes under living conditions.As widely used and powerful tools,biorthogonal reactions are largely defined as “ligation reactions” that are used for labeling,tracing and capturing biomolecules.Recently,an emerging collection of biorthogonal “bond-cleavage reactions” have been developed and applied for biological studies,especially in releasing,activating and manipulating biomolecules.In this review,we will first summarize the characteristics and applications of these biorthogonal cleavage reactions.We will then focus on introducing diverse applications of biorthogonal cleavage reactions,including activation of prodrugs,rescue of intracellular protein activity,engineering of cell surface,among other interesting applications.Finally,the outlook of future development and applications of biorthogonal cleavage reactions will be discussed.