natural motifs into the targeted peptides have been developed (Fig 1a). In this regard, hypervalent iodine reagents (HIR) have been recognized as valuable and versatile reagents for peptide functionalizations due to their low toxicity, high reactivity and good functional group selectivity. They enable the transfer of various electrophiles onto different amino acid residues in peptides or proteins. Among these HIRs, ethynylbenziodoxolones (EBXs) are of particular interest. Nucleophilic amino acid residues or radical species generated under photoredox conditions can be trapped by EBXs to form alkynylation products (Fig ). The introduction of an alkyne can not only provide extra reactive site for further modifications, but also constitutes a unique rigid linker with very low steric demand. Despite these elegant advances, each new transformation required the design of specific reagents and conditions leading to tedious and time-consuming optimizations. Many reagents have also insufficient solubility in water, or display diminished reactivity when modified with water solubilizing groups. In addition, whereas progress has been realized to achieve selective functionalization of one amino acid over others, chemical functionalization methods usually do not allow to select among different sites containing the same residue.