Chemoselective bioconjugation based on modular click chemistry with 4-halocoumarins and aryl sulfonates

We report chemoselective and modular peptide bioconjugation using stoichiometric amounts of 4-halocoumarin and arylsulfonate agents that undergo metal-free C(sp²)-heteroatom bond formation at micromolar concentrations. The underlying ipso-substitution click chemistry is irreversible and generates stable and inherently fluorescent bioconjugates, and the broad selection of coumarin tags offers high labeling flexibility and versatility. Different coumarins and arylsulfonates can be selectively attached to amino and thiol groups in the small peptides glutathione and ornipressin, and both free as well as latent thiols captured in disulfide bridges can be targeted if desired. The broad utility, ease of use, storage, and preparation of 4-halocoumarins and arylsulfonates are very attractive features that extend currently available dual bioconjugation capabilities.