Peptide Stapling Using Sonogashira Coupling

An efficient method for the stapling of peptides by linking residues at the i and i+4 or i and i+7 positions through Sonagashira coupling is reported. The alkyne and aryl iodide functionality required are introduced by modifying tyrosine residues to 4-iodophenylalanine (PhI) and 4-propargyloxyphenylalanine (TyP) residues. Comparing the conformations of a stapled peptide with the corresponding linear peptide using CD spectroscopy reveals a more helical structure for the stapled peptide.