Sulfo DBCO-Maleimide is a water-soluble reagent that enables simple and efficient incorporation of DBCO moiety onto thiol-containing molecules, including cysteine-containing peptides. The sulfonated spacer arm is hydrophilic and greatly improves the solubility of DBCO-derivatized molecules in water and, in many cases, making them also soluble in aqueous buffers. The spacer arm is also short and so, adds minimal mass to modified molecules.