Two antibody-drug conjugates are on the market today, and both of those targeted cancer therapies involve a maleimide, a moiety that readily reacts with thiols. Maleimide linkages aren’t always desirable because they can break apart and recombine with reactive groups in other biomolecules in the body. A team at Scripps Research Institute, La Jolla, Calif., now reports compounds—methylsulfonylphenyloxadiazoles—that complement maleimides by producing a more stable protein-drug linkage (Angew. Chem. Int. Ed. 2013, DOI: 10.1002/anie.201306241). Narihiro Toda, Shigehiro Asano, and Carlos F. Barbas III took inspiration from a heterocyclic reagent that selectively blocks protein thiols. They synthesized a family of similar molecules and, working at physiological pH, determined that methylsulfonylphenyloxadiazoles are selective for cysteine thiols over other reactive moieties in proteins. They made protein conjugates with methylsulfonylphenyloxadiazoles and found that the conjugates were more stable than the corresponding maleimides in human plasma. Researchers’ excitement about drug conjugates has led to several reports of new linkers. The Barbas team adds a brand-new approach that researchers should keep in mind, says Peter D. Senter, vice president of chemistry at the antibody-drug conjugate firm Seattle Genetics. Sigma-Aldrich is commercializing the technology.