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    Prodrugs, which remain inert until they are activated under appropriate conditions at the target site, have emerged as an attractive alternative to drugs that lack selectivity and show off-target effects. Prodrugs have traditionally been activated by enzymes, pH or other trigger factors associated with the disease. In recent years, bioorthogonal chemistry has allowed the creation of prodrugs that can be chemically activated with spatio-temporal precision. In particular, tetrazine-responsive bioorthogonal reactions can rapidly activate prodrugs with excellent biocompatibility. This review summarized the recent development of tetrazine bioorthogonal cleavage reaction and great promise for prodrug systems.


    Yayue Wang, Chang Zhang, Haoxing Wu, Ping Feng. Activation and Delivery of Tetrazine-Responsive Bioorthogonal Prodrugs. Molecules (Basel, Switzerland). 2020 Nov 30;25(23)

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    PMID: 33266075

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