Chemical Biology Lecture: Vinylboronic acids in bioorthogonal chemistry
- Kim Bonger (Radboud University)
- Friday 23 February 2018
2333 CC Leiden
In the last decades, the development of selective chemical reactions that are unaffected by any of the molecular functionalities in cells has been a major focus in chemical biology research. These bioorthogonal reactions require to be high-yielding and rapid while the reactants and products should be stable, soluble and non-toxic to cells. The use of bioorthogonal reactions made it possible to visualize and study biomolecules in their native cellular context and recent developments contributed to advanced targeted drug delivery strategies.
We recently added vinylboronic acids (VBA) as reactants to the bioorthogonal toolbox which react fast with pyridyl tetrazines in an inverse-electron demand Diels-Alder reaction. Depending on the substituents, the non-strained VBA reactants give sufficient reaction rates suitable for bioorthogonal labelling in vitro and in situ. The scope and molecular origins of the observed VBA reactivity and the use with orthogonal reactions for sequential and multiple protein modifications will be presented. In addition, VBAs are explored as chemically-triggered cleavable linkers for targeted drug delivery.
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.
Selma Eising, Nicole van der Linden, Fleur Kleinpenning, Kimberly M. Bonger. Vinylboronic Acids as Efficient Bioorthogonal Reactants for Tetrazine Labeling in Living Cells. Bioconj. Chem. 2018, Accepted Manuscript.