Definition
Solid-phase peptide synthesis, introduced by Bruce Merrifield in 1963, builds a peptide on insoluble resin beads. The C-terminal amino acid is anchored to the resin, and each subsequent residue is added through repeated deprotection and coupling steps, with excess reagents washed away between steps. Because the growing chain stays attached to the solid support, purification during assembly is reduced to simple filtration. When the sequence is complete, the peptide is cleaved from the resin, usually with trifluoroacetic acid, which also removes side-chain protecting groups. Incomplete couplings produce deletion and truncated sequences, which is why crude product is purified by preparative HPLC and then checked by analytical HPLC and mass spectrometry.