Amino Acids for Diels–Alder Reactions in Living Cells

Under tension: A set of genetically encoded unnatural amino acids can be used for biocompatible site-specific labeling of proteins with fluorogenic dyes. The new compounds have norbornene and trans-cyclooctene units that react with tetrazine derivatives in an inverse-electron-demand Diels–Alder cycloaddition (left in picture). The technique offers fast labeling that is orthogonal to labeling through azide–cyclooctyne click reaction (right).