A universal strategy for preparing protected C-terminal peptides on the solid phase through an intramolecular click chemistry-based handle.

A new universal strategy exploits DKP formation in a dipeptide moiety whose C-terminal residue is blocked by a leaving group. It enables both synthesis of C-terminal protected peptides that are useful for convergent synthesis of large peptides and use of a C-terminal permanent protecting group that can be cleaved by catalytic hydrogenation to release the peptide.