ω-Conotoxin MVIIA is the main component of Ziconotide, a therapeutic drug on the market as treatment of chronic pain. It is difficult to be synthesized by using standard Fmoc strategy solid phase peptide synthesis (SPPS) on polystyrene resin. ω-MVIIA is a typical "difficult sequence" for SPPS. In this work, N-terminal 15-residue peptide thioester and C-terminal 10-residue peptide amide of ω-MVIIA were synthesized using standard Fmoc protocol respectively. The full-length chain of ω-MVIIA was prepared by native chemical ligation. This method increased the yield of ω-MVIIA greatly. The results provide a good reference for synthesis of "difficult sequence".

Key words: native chemical ligation, peptide thioester, peptide synthesis, ω-conotoxin MVIIA