Next, the covalent labeling nature of the DZE probe was explored by performing peptide mapping of CA after electrolysis with 15. LC-MS/MS analysis showed modification of a diverse set of amino acids surrounding the entrance of the zinc binding pocket that include multiple aspartate, glutamate, and lysine residues, as well as minimally detected labeling of valine, glycine and phenylalanine (Figure ). As a comparison, photoaffinity labeling (PAL) was performed using a broadly utilized, fully functionalized dialkyl diazirine probe containing design features similar to our DZE probe 15. UV irradiation of the CA-diazirine probe 16 in the presence of CA resulted in labeling near the active site entrance similar to the DZE probe but with different residue labeling patterns that primarily includes glutamate and aspartate residues (Figure ). This carboxylate side chain preference achieved by 16 was consistent with recent studies using a dialkyl diazirine probe, highlighting the restricted amino acid residue reactivity profile for this commonly used PAL reagent. Thus, while both probes label within similar regions of the targeted protein, the broader amino acid labeling coverage achieved by the DZE probe facilitates increased opportunities for covalent protein capture within complex environments.