Publisher Summary In solid-phase peptide synthesis, protein is synthesized by the successive addition of appropriately protected amino acid residues to a completely insoluble growing point. The majority of peptides prepared by solid-phase techniques have been synthesized in a stepwise fashion with progression from the COOH-terminal to the NH 2 -terminal residue. The scheme for stepwise progression involves five steps. The first reaction results in an attachment of the COOH-terminal residue to the solid support. Second step involves deprotection which uncovers the α-NH 2 group of the COOH-terminal residue for subsequent peptide bond formation with the carboxyl group of the penultimate residue. Third step includes neutralization and subsequent step involves coupling. Steps 2, 3, and 4 are then carried out for each successive residue in the peptide until the addition of the NH 2 -terminal residue is completed. At this point, the completed peptide is cleaved from the solid support (step 5). The specific reaction used again depends upon the choice of the support; the structure of the desired peptide and the nature of the side-chain blocking groups will also be factors in determining the nature of the cleavage reaction. The success of a stepwise solid-phase peptide synthesis is critically dependent upon the attainment of very high yields at steps 2, 3, and 4.