Oliveira, Bruno L.Guo, ZijianBoutureira, OmarGuerreiro, AnaJiménez‐Osés, GonzaloBernardes, Gonçalo J. L.2022-01-182022-01-182016Angew Chem Int Ed Engl. 2016 Nov 14;55(47):14683-146871433-7851http://hdl.handle.net/10451/50878© 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.The unstrained S-allyl cysteine amino acid was site-specifically installed on apoptosis protein biomarkers and was further used as a chemical handle and ligation partner for 1,2,4,5-tetrazines by means of an inverse-electron-demand Diels-Alder reaction. We demonstrate the utility of this minimal handle for the efficient labeling of apoptotic cells using a fluorogenic tetrazine dye in a pre-targeting approach. The small size, easy chemical installation, and selective reactivity of the S-allyl handle towards tetrazines should be readily extendable to other proteins and biomolecules, which could facilitate their labeling within live cells.engDiels-Alder reactionsApoptosisBioorthogonal labelingPre-targetingUnstrained alkenesjournal article10.1002/anie.2016084381521-3773