Selective chemical reactions that are unaffected by any of the molecular functionalities in cells has been a major field of chemical biology research. These so-called bioorthogonal reactions require that they are high yielding and rapid, and the reactants and product should be stable in aqueous media. In addition, when one of the reactants is incorporated in a biomolecule the size should be small to minimize interactions with the biomolecule.
In our research, we are exploring vinyl boronic acids (VBA) as new bioorthogonal reaction partner with tetrazines. Compared to other tetrazine-reactive bioorthogonal reactants, VBAs are especially unique as they are non-strained, hydrophilic and highly stable in cells. We are exploring the scope and unique reactivity of VBAs towards tetrazines and apply these for selective labeling of biomolecules in live cells.
We have found that VBAs are especially reactive towards tetrazines containing Lewis-basic substituents while they are inactive towards tetrazines lacking such substituent. This unique feature allows the selective orthogonal reaction of VBAs with these coordinating tetrazines in the presence of tetrazine-reactive strained alkenes.
Current research is directed at understanding and optimizing the VBA reactivity with coordinating tetrazines in more detail and applying the reaction for imaging and therapeutic applications.