Photoisomerization-enhanced 1,3-dipolar cycloaddition of carbon-bridged octocyclic azobenzene with photo-released nitrile imine for peptide stapling and imaging in live cells

Abstract

A photo-induced 1,3-dipolar cycloaddition between nitrile imine and highly ring-strained N[double bond, length as m-dash]N double bond as a dipolarophile was discovered. The photo-isomerization of carbon-bridged octocyclic azobenzene (CBOA) into its trans-configuration accelerates the ligation reaction at a very rapid rate (28 400 M^-1 s^-1). The CBOA-based photo-click reaction was proved to be bioorthogonal. In addition, the NoxaB peptide was successfully cross-linked by a CBOA stapler which plays a dual role: photo-control of the conformation of the peptide and photo-conjugation of probes in live cells.