Cys–Cys and Cys–Lys Stapling of Unprotected Peptides Enabled by Hypervalent Iodine Reagents

Easy access to a wide range of structurally diverse stapled peptides is crucial for the development inhibitors protein-protein interactions. Herein, we report bis-functional hypervalent iodine reagents two-component cysteine-cysteine and cysteine-lysine stapling yielding thioalkyne linkers. This method works with unprotected natural amino acid residues does not require pre-functionalization or metal catalysis. The products are stable purification isolation. Post-stapling modification can be accessed via amidation an activated ester, cycloaddition onto formed group. Increased helicity binding affinity MDM2 was obtained i,i+7 peptide.