Bioorthogonal chemistry: Bridging chemistry, biology, and medicine

Abstract

As chemical biologists sought methods to modify and study biomolecules in their native environments, the need for bioorthogonal chemical reactions emerged. These fast and selective reactions between otherwise inert, abiotic functional groups have enabled exploration of some of the most intriguing and challenging questions in chemical biology. Further, the ability to perform organic reactions in cells and organisms has led to important applications in clinical spaces, and one reaction is now an integral part of a phase 2 trial for treating solid tumors. Given that bioorthogonal chemistry was a recipient of the 2022 Nobel Prize, we expect this field to be even more energized. Here, we highlight some of the most recent studies in this sphere and how these set the stage for where bioorthogonal chemistry is headed. As chemical biologists sought methods to modify and study biomolecules in their native environments, the need for bioorthogonal chemical reactions emerged. These fast and selective reactions between otherwise inert, abiotic functional groups have enabled exploration of some of the most intriguing and challenging questions in chemical biology. Further, the ability to perform organic reactions in cells and organisms has led to important applications in clinical spaces, and one reaction is now an integral part of a phase 2 trial for treating solid tumors. Given that bioorthogonal chemistry was a recipient of the 2022 Nobel Prize, we expect this field to be even more energized. Here, we highlight some of the most recent studies in this sphere and how these set the stage for where bioorthogonal chemistry is headed. The certainty of a few good reactionsMoorhouse et al.ChemApril 19, 2023In BriefThe 2022 Nobel Prize in Chemistry was the crowning glory for the already vindicated field of click chemistry. At its heart, the click approach toward discovering functional molecules relies upon the dependability of a core family of privileged chemical reactions. Focusing on what we believe are significant developments that enrich the click chemistry toolbox from the perspective of medicinal chemistry, we hope this account inspires the search for new functions and click chemistries. Full-Text PDF Bioorthogonal reactions and AIEgen-based metabolically engineered theranostic systemsKenry et al.ChemMay 4, 2023In BriefMetabolic labeling based on bioorthogonal click chemistry has transformed the way living entities are manipulated in biological environments. Since the initial demonstrations of this method, numerous metabolic-labeling strategies have been formulated, including those leveraging fluorogens with aggregation-induced emission characteristics (AIEgens). In this perspective, we discuss various aspects of the development of AIEgen-based bioorthogonal metabolically engineered theranostic systems—including their design principles, formulation, and applications for different disease theranostics—current challenges, and future opportunities. Full-Text PDF