Journal
ACS CENTRAL SCIENCE
Volume 7, Issue 6, Pages 929-943Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acscentsci.1c00124
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Funding
- National Key Research and Development Program of China [2016YFA0501500, 2019YFA0904201]
- National Natural Science Foundation of China [21521003, 21740001, 21937001, 91957101, 22077004, 22077059]
- Beijing National Laboratory for Molecular Sciences [BNLMS202012]
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Bioorthogonal cleavage chemistry, as a powerful tool for manipulation and gain-of-function studies of biomolecules, has opened up new possibilities for rescuing small molecules and biomacromolecules, allowing multidimensional control over biological processes.
Bioorthogonal cleavage chemistry has been rapidly emerging as a powerful tool for manipulation and gain-of-function studies of biomolecules in living systems. While the initial bond formation-centered bioorthogonal reactions have been widely adopted for labeling, tracing, and capturing biomolecules, the newly developed bond cleavage-enabled bioorthogonal reactions have opened new possibilities for rescuing small molecules as well as biomacromolecules in living systems, allowing multidimensional controls over biological processes in vitro and in vivo. In this Outlook, we first summarized the development and applications of bioorthogonal cleavage reactions (BCRs) that restore the functions of chemical structures as well as more complex networks, including the liberation of prodrugs, release of bioconjugates, and in situ reactivation of intracellular proteins. As we embarked on this fruitful progress, we outlined the unmet scientific needs and future directions along this exciting avenue. We believe that the potential of BCRs will be further unleashed when combined with other frontier technologies, such as genetic code expansion and proximity-enabled chemical labeling.
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