Phototriggers Track Protein Dynamics

Novel tetrazine-based probes that can be selectively inserted into peptides and removed photochemically open a new window into peptide conformational dynamics (Angew. Chem. Int. Ed., DOI: 10.1002/anie.201000500). Several photochemical agents have previously been designed to be incorporated into a peptide to constrain the structure and then to be removed photochemically, releasing the constraint and allowing the kinetics of the resulting peptide rearrangements to be monitored. Some of these probes need to be triggered with UV radiation, which can produce harmful radical by-products, and others introduce unwanted constraints on the structure of the generated peptide. Amos B. Smith III, Robin M. Hochstrasser, and coworkers at the University of Pennsylvania have devised tetrazine phototriggers that sidestep these complications. The new triggers can be photolyzed by visible or UV pulses, their photoproducts are only nitrogen and inert nitriles, and they introduce no unwanted constraints on generated peptides. The researchers suggest that the probes will permit tracking of peptide structure evolution at the amino acid residue level by 2-D vibrational spectroscopy.