Liu, Xing-YuJi, XinjianHeinis, ChristianWaser, Jerome2023-08-142023-08-142023-08-142023-07-0710.1002/anie.202306036https://infoscience.epfl.ch/handle/20.500.14299/199726WOS:001030362200001Herein, we report a novel strategy for the modification of peptides based on the introduction of highly reactive hypervalent iodine reagents-ethynylbenziodoxolones (EBXs)-onto peptides. These peptide-EBXs can be readily accessed, by both solution- and solid-phase peptide synthesis (SPPS). They can be used to couple the peptide to other peptides or a protein through reaction with Cys, leading to thioalkynes in organic solvents and hypervalent iodine adducts in water buffer. Furthermore, a photocatalytic decarboxylative coupling to the C-terminus of peptides was developed using an organic dye and was also successful in an intramolecular fashion, leading to macrocyclic peptides with unprecedented crosslinking. A rigid linear aryl alkyne linker was essential to achieve high affinity for Keap1 at the Nrf2 binding site with potential protein-protein interaction inhibition.Chemistry, MultidisciplinaryChemistryhypervalent iodine reagentspeptideprotein modificationpeptide macrocyclizationkeap1-nrf2 protein-protein interaction inhibitorsethynyl benziodoxoloneclick chemistrycyclic peptidediscoveryalkynylationtryptophanproteinsenamidesvinyltext::journal::journal article::research article