Methanethiosulfonates (MTS) are sulfhydryl-reactive compounds that form mixed disulfide linkages and are commonly used to study cysteine residues on proteins. Sodium (2-sulfonatoethyl)methanethiosulfonate (MTSES) is a negatively-charged, membrane impermeant MTS. It is highly reactive with ionized thiolates but not with unionized thiols and, therefore, targets sulfhydryl groups accessible from the aqueous medium. MTSES is used to probe the structural and functional properties of native proteins, particularly those associated with membranes, including channels and transporters. In addition, charged MTS compounds like MTSES are combined with cysteine scanning mutagenesis to study non-cysteine residues.
