Linking peptide therapeutics to molecules such as polyethylene glycols (PEGs) is a useful way to control their bioactivity, so drugmakers constantly seek new ways to build so-called peptide conjugates. The well-known click reaction, a copper-catalyzed cycloaddition of azides and alkynes, rapidly attaches moieties to peptides without disturbing unprotected functional groups. However, it generates an unnatural linkage and can require an excess of one reagent, an impractical option when some PEGs cost as much as their peptide partners. To address these challenges, Jeffrey W. Bode and colleagues at ETH Zurich have developed a reaction that forms amides from the union of potassium acyltrifluoroborates to O-carbamoylhydroxylamines incorporated into peptides (J. Am. Chem. Soc. 2014, DOI: 10.1021/ja5018442). The reaction works in water with a 1:1 ratio of reagents. Bode’s team used it to attach biotin, PEG, a fluorescent dye, or a lipid to an antidiabetes peptide. “This bioorthogonal reaction is distinguished because it is both fast and also produces native amide bonds,” says the University of Delaware’s Joseph M. Fox, who has also developed protein-tagging methods. ETH has filed a patent application covering PEG attachment with this chemistry.