Peptide Synthesis

Peptide synthesis is the production of peptides by forming amide (peptide) bonds between amino acids in a defined sequence. The dominant method is solid-phase peptide synthesis (SPPS), developed by Bruce Merrifield in 1963, in which the C-terminal amino acid is anchored to an insoluble resin bead and the peptide chain is extended one residue at a time from C-terminus to N-terminus. Each coupling cycle involves deprotection of the alpha-amino group, activation of the incoming amino acid carboxyl group, and formation of the peptide bond, followed by washing to remove excess reagents. After chain assembly, the peptide is cleaved from the resin and side-chain protecting groups are removed simultaneously. Modern SPPS employs either Fmoc (base-labile) or Boc (acid-labile) protecting group strategies, with Fmoc being preferred for most research-grade peptides due to milder reaction conditions. Following synthesis, peptides undergo purification by HPLC and characterisation by mass spectrometry to verify identity, purity, and correct sequence, as required by ORYN quality protocols.