Speaker: Dr. Kimberly M. Bonger. Department of Biomolecular Chemistry, Radboud University, Nijmegen, The Netherlands
Organizers: IRB Barcelona
Date: Thursday, 25 October, 09:30h
Place: Serratosa Room, Parc Científic de Barcelona
Host: Dr. Antoni Riera, IRB Barcelona
The 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. Recent developments in the field provided orthogonal bioorthogonal reactions for modification of multiple biomolecules simultaneously. 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-s-tetrazines relative to that of tetrazines lacking such dative ligand. As VBAs are mild Lewis acids, we hypothesize that coordination of the pyridyl nitrogen to the boronic acid promotes the tetrazine ligation. We here explore the scope and molecular origins of the observed VBA reactivities in more detail and benefit from its unique reactivity in the simultaneous orthogonal tetrazine labelling of two proteins. In addition, we further evaluated the VBA toolbox as chemically-triggered cleavable linkers for targeted drug delivery.
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, 19, 1648.
Chemistry and Molecular Pharmacology Programme Seminar