Vinylboronic Acids as Fast Reacting, Synthetically Accessible, and Stable Bioorthogonal Reactants in the Carboni-Lindsey Reaction.

Bioorthogonal reactions are widely used for the chemical modification of biomolecules. The application of vinylboronic acids (VBAs) as non-strained, synthetically accessible and water-soluble reaction partners in a bioorthogonal inverse electron-demand Diels-Alder (iEDDA) reaction with 3,6-dipyridyl-s-tetrazines is described. Depending on the substituents, VBA derivatives give second-order rate constants up to 27 m(-1) s(-1) in aqueous environments at room temperature, which is suitable for biological labeling applications. The VBAs are shown to be biocompatible, non-toxic, and highly stable in aqueous media and cell lysate. Furthermore, VBAs can be used orthogonally to the strain-promoted alkyne-azide cycloaddition for protein modification, making them attractive complements to the bioorthogonal molecular toolbox.