Bis-sulfone-PEG4-NHS ester is a bifunctional alkylating labeling reagent that selectively removes cysteine sulfur atoms from native disulfide bonds. These reagents perform bis-alkylation to attach both thiols from two cysteine residues, originating from reduced native disulfide bonds (such as interchain disulfide bonds in antibodies). The reaction results in a covalent bond through a three-carbon bridge, maintaining the protein's structural integrity. The hydrophilic PEG spacer enhances its solubility in aqueous media.