As further demonstration of the versatility of this electrochemical labeling approach, four additional small molecule ligand scaffolds (dasatinib, VX680, JQ-1, and PD0325901) were studied. The DZE functional group was appended to each of the inhibitors to prepare 17-20, and subsequently incubated in the presence of their respective binding proteins ABL, AURKA, BRD4, and MEK1. Electrochemically dependent desthiobiotinylation was detected for each of these protein/DZE-ligand pairs that could be competed away in the presence of excess free ligand (Figure ). Importantly, similar to the CA labeling experiment in Figure , the labeling effect was specific to the target protein as no off-target protein labeling was observed in the presence of a bystander protein (Figure ). Additionally, to investigate the ligand compatibility of our ECAL ) using 1 min of electrochemical-or UV-activation, respectively. Labeled residues are highlighted on the protein and by bar plot analysis that shows residue number (x-axis) and spectral counts (y-axis) of labeled peptide containing the modification. D) Electroaffinity labeling of ABL, AURKA, BRD4, and MEK1 proteins using known small molecule ligands linked with DZE. Western blot analysis shows electrochemically dependent desthiobiotinylation that can be competed away with excess free ligand.