Figure 1.
(a) Bioorthogonal ligation of tetrazines (Tz) and trans-cyclooctenes (TCO) for the fluorogenic labeling of biomolecules, targeting compounds or ligands (top) and Tz-triggered cleavage from trans-cyclooctene modified in allylic position (release-TCO, rTCO) for the bioorthogonal activation of prodrugs or rTCO-caged biomolecules (bottom). (b) Concept of bioorthogonal cleavage to disassemble molecular probes (top) or inactivate fused biomolecules. (c) Limitations of the IEDDA pyridazine elimination with emphasis on Tz/TCO click rates, release yield, and release kinetics.