By modifying the fastest and highly selective click reaction, the inverse-electron-demand-Diels-Alder reaction, Tagworks has achieved selective bioorthogonal release. This holds promise for the chemically triggered release, and thus activation, of drugs from tumor-bound Antibody-Drug Conjugates (ADCs), which would greatly enhance the scope of suitable ADC targets. Published in: Angewandte Chemie online 26 Nov 2013 - doi:10.1002/anie.201305969