Strain-promoted sydnone bicyclo-[6.1.0]-nonyne cycloaddition†Electronic supplementary information (ESI) available: Full experimental details, H/C NMR spectral data, protein synthesis and purification. See DOI: 10.1039/c3sc53332h.

The discovery and exploration of bioorthogonal chemical reactions and the biosynthetic incorporation of their components into biomolecules for specific labelling is an important challenge. Here we describe the reaction of a phenyl sydnone 1,3-dipole with a bicyclononyne dipolarophile. This strain-promoted reaction proceeds without transition metal catalysis in aqueous buffer, at physiological temperature, and pressure with a rate comparable to that of other bioorthogonal reactions. We demonstrate the quantitative and specific labelling of a genetically encoded bicyclononyne with a sydnone fluorophore conjugate, demonstrating the utility of this approach for bioorthogonal protein labelling.