Synthetic strategies
to assemble peptide fragments are in high
demand to access homogeneous proteins for various applications. Here,
we combined native chemical ligation (NCL) and Pd-mediated Cys arylation
to enable practical peptide ligation at aromatic junctions. The utility
of one-pot NCL and S-arylation at the Phe and Tyr junctions was demonstrated
and employed for the rapid chemical synthesis of the DNA-binding domains
of the transcription factors Myc and Max. Organometallic palladium
reagents coupled with NCL enabled a practical strategy to assemble
peptides at aromatic junctions.