Synthesis of Proteins by Native Chemical Ligation Using Fmoc-Based Chemistry

C-terminal peptide α-thioesters are valuable intermediates in the synthesis/semisynthesis of proteins by native chemical ligation. They are prepared either by solid-phase peptide synthesis (SPPS) or biosynthetically by protein splicing techniques. The present paper reviews the different methods available for the chemical synthesis of peptide α-thioesters using Fmoc-based SPPS. Keywords: chemical protein synthesis, native chemical ligation, peptide thioester, hydrazine linker, protein engineering, fmoc-chemistry