Organelle-specific prodrug activation

29 December 2020
Organelle-specific prodrug activation
Overview of the workflow leading to the development of mitochondria-specific bioorthogonal release reaction. Mitochondriotropic tetrazines are selected from a pool of tetrazines based on the right combination of lipophilicity and positive delocalized charge. After addition to cells, the optimized tetrazine reagents react with TCO-caged compounds, enabling their reactivation in a mitochondria-specific manner.

Many drug targets are located in particular cellular compartments known as organelles. Traditional medicinal chemistry approaches focus on bioavailability and tissue targeting, but rarely address drug delivery to specific cellular organelles. Our team has demonstrated that the delivery and release of biologically active molecules from inactive precursors can be achieved in an organelle-specific manner.

Read more in the IOCB web article.

  • R. Dzijak, J. Galeta, A. Vázquez, J. Kozák, M. Matoušová, H. Fulka, M. Dračínský, M. Vrábel, Structurally Redesigned Bioorthogonal Reagents for Mitochondria-Specific Prodrug Activation, JACS Au 2020, https://pubs.acs.org/doi/full/10.1021/jacsau.0c00053
An artistic rendering by Tomáš Belloň from IOCB Prague of a prodrug and its activator penetrating the membrane into a cell, meeting in the mitochondria, reacting with each other, and releasing an active molecule. (Graphic design: Tomáš Belloň / IOCB Prague)
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