Herein, 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 easily accessed, both via solution and solid phase peptide synthesis (SPPS). They can be used to couple the peptide to other peptides or a protein via reaction with cysteine, leading to thioalkynes in organic solvents and hypervalent iodine adducts in water buffer. In addition, a photocatalytic decarboxylative coupling to the C-terminus of peptides was developed using an organic dye. This later reaction was also successful in an intramolecular way, leading to macrocyclic peptides of an unprecedented shape. The rigid linear aryl alkyne linker was essential to achieve high affinity to Keap1 at the Nrf2 binding site with potential protein-protein interaction inhibition.
Supporting Information for article Peptide-EBXs: Enabling Peptide Functionalization and Macrocyclization
General procedures, HPLC and MS methods, Synthetic procedures, TR-FRET assay, characterization data and copy of NMR spectra