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Theme 2 colloquium: "Coordination-Assisted Bioorthogonal Chemistry: Bringing Orthogonality in the Tetrazine Ligation with (strained) alkenes" (Lecture)

Tuesday 14 May 2019Add to my calendar
from 16:00
dr. Kim Bonger (Synthetic Organic Chemistry)

Kim BongerThe development of bioorthogonal reactions made it possible to visualize and study biomolecules in their native cellular context and contributed to advanced targeted drug delivery strategies. In our research group we are interested in developing novel bioorthogonal chemistry and apply this in the targeting of specific cell types. We recently added non-strained, highly soluble and stable vinylboronic acids (VBA) as reactants to the bioorthogonal toolbox which react with tetrazines in an inverse-electron demand Diels-Alder reaction. We have observed exceptional high reaction rates between non-strained vinylboronic acids (VBAs) and dipyridyl tetrazines relative to that of tetrazines lacking such dative coordinating ligand. As VBAs are mild Lewis acids, we hypothesize that coordination of the pyridyl to the boronic acid promotes the tetrazine ligation. In the current presentation, we explore the scope and molecular origins of the observed VBA reactivity in more detail and benefit from its unique properties in the simultaneous orthogonal tetrazine labelling of proteins. In addition, we further extended the VBA toolbox as chemically-triggered cleavable linkers for targeted drug delivery with the specific focus on autoreactive B-cells.

1) Selma Eising, Francis Lelivelt, Kimberly M. Bonger*. Vinylboronic Acids as Fast Reacting, Synthetically Accessible, and Stable Bioorthogonal Reactants in the Carboni–Lindsey Reaction. Angew. Chem. Int. Ed. 2016, 55, 12243.
2) Selma Eising, Nicole van der Linden, Fleur Kleinpenning, Kimberly M. Bonger. Vinylboronic Acids as Efficient Bioorthogonal Reactants for Tetrazine Labeling in Living Cells. Bioconjug. Chem. 2018, 29, 982.
3) Selma Eising, Bo-Tao Xin, Fleur Kleinpenning, Jurriaan J. A. Heming, Bogdan I. Florea, Herman S. Overkleeft and Kimberly M. Bonger* Coordination-Assisted Bioorthogonal Chemistry: Orthogonal Tetrazine Ligation with Vinylboronic Acid and a Strained Alkene, ChemBioChem 2018, 15, 1648.

dr. Evan Spruijt & dr. Peter Korevaar