Peptide-Hypervalent Iodine Reagent Chimeras: Enabling Peptide Functionalization and Macrocyclization** |
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Authors: | Xing-Yu Liu Dr Xinjian Ji Prof Dr Christian Heinis Prof Dr Jerome Waser |
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Institution: | 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 |
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Abstract: | 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 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. |
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Keywords: | Hypervalent Iodine Reagents Peptide/Protein Modification Peptide Macrocyclization Keap1-Nrf2 Protein-Protein Interaction Inhibitors |
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