Investigating the Bio-orthogonality of Isocyanides

Isocyanides have been applied in bio-orthogonal reactions as triggers for uncaging reactions. However, emerging evidence suggests that they may label proteins covalently and are not bio-orthogonal.1 We synthesized a fluorophore-bound isocyanide and analysed its protein reactivity. Our results suggest that isocyanides cannot be considered to be bio-orthogonal in chemical biology.