Sulfo TCO-Maleimide is a water-soluble reagent that enables simple and efficient incorporation of TCO moiety onto thiol-containing molecules, including cysteine-containing peptides. The maleimide group specifically and efficiently reacts with reduced thiols (sulfhydryl groups, –SH) at pH 6.5-7.5 to form stable thioether bonds. The sulfonated spacer arm is hydrophilic and greatly improves the solubility of TCO-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.