Merrifield Solid‐Phase Peptide Synthesis

Abstract The synthesis of peptides and small proteins in which the resinous polymer supported amino acid and succeeding peptide repeatedly reacts with N ‐protected amino acids followed by deprotection until the desired peptide or protein is assembled is generally referred to as the Merrifield solid phase peptide synthesis (or SPPS) and the polymeric resin is known as the Merrified resin. The initial protocol using N ‐benzyloxycarbonyl‐protected amino acid has been improved and developed into two complementary methods. In the first method the N ‐ t ‐butyloxycarbonyl (Boc) protected amino acid is attached to the solid phase via a linker moiety and the second protocol uses 9‐fluorenylmethyloxycarbonyl (Fmoc) as the amino protecting group, which can be easily cleaved. It has been found that the ongoing peptide chain may stop growing or lead to a low yield of peptide, due to the association of the peptide chain, the swelling problem of the resin, etc. The study finds that application of a mixed solvent of CH 2 Cl 2 and DMF apparently enhances the result. This reaction has been applied for the preparation of peptides and small proteins.