Bis-sulfone-PEG8-NHS ester is a bis-alkylating labeling agent that selectively removes cysteine sulfur atoms from native disulfide bonds. These agents achieve bis-alkylation by covalently bridging the two thiols from cysteine residues derived from reduced native disulfide bonds, such as interchain disulfide bonds in antibodies, through a three-carbon bridge while maintaining the integrity of the protein structure. The hydrophilic PEG spacer enhances solubility in aqueous media.