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Issue 39, 2019
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Vinylboronic acid-caged prodrug activation using click-to-release tetrazine ligation

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Abstract

Bioorthogonal reactions can be performed selectively in the presence of any biological functional group and are widely used to achieve site-selective chemical modifications of biomolecules. The click-to-release reaction is a bioorthogonal bond-cleavage variant that has gained much interest over the last few years. The bioorthogonal reaction between tetrazines and trans-cyclooctenes or vinyl ethers, for example, initiates the release of a small molecule immediately after the cycloaddition with tetrazines. Recently, our group reported that vinylboronic acids (VBAs) give exceptionally high reaction rates in the bioorthogonal inverse electron-demand Diels–Alder reaction with tetrazines that are substituted with boron-coordinating ligands. In the present study, we show that VBAs can be used in a click-to-release variant and demonstrate its bioorthogonality with a VBA-protected doxorubicin prodrug. We show that the cytotoxicity of doxorubicin is silenced by the attachment of the VBA, and activity can be largely restored upon the reaction with a tetrazine, inducing cell death.

Graphical abstract: Vinylboronic acid-caged prodrug activation using click-to-release tetrazine ligation

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Publication details

The article was received on 27 Aug 2019, accepted on 17 Sep 2019 and first published on 17 Sep 2019


Article type: Communication
DOI: 10.1039/C9OB01881F
Org. Biomol. Chem., 2019,17, 8816-8821
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    Vinylboronic acid-caged prodrug activation using click-to-release tetrazine ligation

    L. P. W. M. Lelieveldt, S. Eising, A. Wijen and K. M. Bonger, Org. Biomol. Chem., 2019, 17, 8816
    DOI: 10.1039/C9OB01881F

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