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.[1][2][3] In addition, charged MTS compounds like MTSES are combined with cysteine scanning mutagenesis to study non-cysteine residues.[4][5]

Reference：
[1]. Lang, R.J., Harvey, J.R., and Mulholland, E.L. Sodium (2-sulfonatoethyl) methanethiosulfonate prevents S-nitroso-L-cysteine activation of Ca2+-activated K+ (BKCa) channels in myocytes of the guinea-pig taenia caeca. Br. J. Pharmacol. 139(6), 1153-1163 (2003).
[2]. Li, R.A., Tsushima, R.G., Kallen, R.G., et al. Pore residues critical for μ-CTX binding to rat skeletal muscle Na+ channels revealed by cysteine mutagenesis. Biophys. J. 73(4), 1874-1884 (1997).
[3]. Guan, L., and Kaback, H.R. Site-directed alkylation of cysteine to test solvent accessibility of membrane proteins. Nature Protocols 2(8), 2012-2017 (2007).
[4]. Engh, A.M., and Maduke, M. Cysteine accessibility in ClC-0 supports conservation of the ClC intracellular vestibule. Journal of General Physiology 125(6), 601-617 (2014).
[5]. Liu, X., Alexander, C., Serrano, J., et al. Variable reactivity of an engineered cysteine at position 338 in cystic fibrosis transmembrane conductance regulator reflects different chemical states of the thiol. The Journal of Biological Chemisty 281(12), 8275-8285 (2006).