Highly Stable and Selective Tetrazines for the Coordination-Assisted Bioorthogonal Ligation with Vinylboronic Acids.

ABSTRACT: Bioorthogonal reactions are selective transformations that are not affected by any biological functional group and are widely used for chemical modification of biomolecules. Recently, we reported that vinylboronic acids (VBAs) gave exceptionally high reaction rates in the bioorthogonal inverse electron-demand Diels-Alder (iEDDA) reaction with tetrazines bearing a boron-coordinating pyridyl moiety compared to tetrazines lacking such a substituent. In this integrated experimental and theoretical study, we show how the reaction rate of the VBA-tetrazine ligation can be accelerated by shifting the equilibrium from boronic acid to the boronate anion in the reaction mixture. Quantum chemical activation strain analyses reveal that this rate enhancement is a direct consequence of the excellent ele

SUBMITTER: Eising S 

PROVIDER: S-EPMC6148442 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature