Bis-sulfone-PEG4-TCO is a bis-alkylating labeling reagent that is selective for the cysteine sulfur atoms from a native disulfide. These reagents undergo bis-alkylation to conjugate both thiols derived from the two cysteine residues of a reduced native disulfide bond such as the interchain disulfide bonds of an antibody. The reaction results in covalent rebridging of the disulfide bond via a three carbon bridge leaving the protein structurally intact. TCO enables fast click chemistry with tetrazine under mild conditions. The hydrophilic PEG spacer increases solubility in aqueous media.
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