Bioorthogonal Chemistry in Translational Research: Advances and Opportunities

Abstract Bioorthogonal chemistry is a rapidly expanding field of research that involves the use of small molecules that can react selectively with biomolecules in living cells and organisms, without causing any harm or interference with native biochemical processes. It has made significant contributions to the field of biology and medicine by enabling selective labeling, imaging, drug targeting, and manipulation of bio‐macromolecules in living systems. This approach offers numerous advantages over traditional chemistry‐based methods, including high specificity, compatibility with biological systems, and minimal interference with biological processes. In this review, we provide an overview of the recent advancements in bioorthogonal chemistry and their current and potential applications in translational research. We present an update on this innovative chemical approach that has been utilized in cells and living systems during the last five years for biomedical applications. We also highlight the nucleic acid‐templated synthesis of small molecules by using bioorthogonal chemistry. Overall, bioorthogonal chemistry provides a powerful toolset for studying and manipulating complex biological systems, and holds great potential for advancing translational research.