Affiliation:
1. Laboratory of Catalysis and Organic Synthesis Ecole Polytechnique Fédérale de Lausanne EPFL 1015 Lausanne Switzerland
2. Laboratory of Therapeutic Proteins and Peptides Ecole Polytechnique Fédérale de Lausanne EPFL 1015 Lausanne Switzerland
Abstract
AbstractHerein, 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.
Funder
HORIZON EUROPE European Research Council