Bioorthogonal Cleavage Chemistry: Harnessing the Bond‐Break Reactions for Biomolecule Manipulations in Living Systems

作者：Yuchao Zhu, Feng Lin, Ziqi Liu, Xin Wang, Shubing Wang, Xinyuan Fan, Peng R. Chen · 发表于：Chinese Journal of Chemistry · 年份：2024 · DOI：10.1002/cjoc.202400876 · 被引用次数：18 · 研究领域：Click Chemistry and Applications、Chemical Synthesis and Analysis、Monoclonal and Polyclonal Antibodies Research

Comprehensive Summary The advancement of bioorthogonal cleavage reactions (BCRs) has expanded the scope of the bioorthogonal chemistry toolkit, leading to a diverse array of innovative biological applications. These include but are not limited to precise spatial and temporal activation of intracellular probes, prodrugs, proteins, glycans, and nucleic acids. Herein, we summarize recent efforts by our group to develop BCRs for manipulating functional molecules in living species to meet various needs, along with future perspectives in this exciting field. How do you get into this specific field? Could you please share some experiences with our readers? Chemists are good at both forming and breaking bonds. Back in 2013, while the field of bioorthogonal reactions was continuously thriving, most researchers focused on the "ligation" type of bioorthogonal reactions. Alternatively, I started to wonder whether we could develop the "bond‐cleavage" type of bioorthogonal reactions? We reviewed the literature and found that this is indeed a field that is yet to be developed. I immediately encouraged my graduate students to develop such reactions while I began to look for potential applications for such new chemistry. We soon developed a series of bioorthogonal "cleavage" reactions that can be triggered by metals, small molecules, as well as photocatalysis. We then applied these reactions to activate proteins and other biomolecules, allowing the gain‐of‐function study of their properties i...