Tunable and stable TAREs for targeting lysine. (a) Structures of a variety of TAREs with different modifications to interrogate their reactivity and selectivity for lysine. (b) Screening of TAREs to determine high selectivity for lysine by using peptide FKVCF 2a with all the nucleophilic residues. Probe 1d showed high selectivity and reactivity for lysine. (c) Reactivity of cysteine-TARE conjugate towards lysine to generate stable product. (d) Modification of proteins with various TAREs. These proteins do not have any cysteine residue and TAREs showed high selectivity for lysine as analyzed by LC-MS/MS. Reaction Conditions: protein (3 mM in Nap (pH 7.5), probe 1d (10 equiv., 30 mM), 1e (100 equiv., 300mM), room temperature for 1h, detection wavelength 200 nm. For lb and CyC modification, probe 1 equiv. of 1d (3 mM) was used for 1h.