Glossary
Solid-Phase Peptide Synthesis (SPPS)
SPPS assembles a peptide on resin from the C-terminus, with one deprotect-and-couple cycle per residue. Why coupling efficiency caps the purity you can reach.
Solid-phase peptide synthesis was introduced by Bruce Merrifield in 1963 and earned him the 1984 Nobel Prize in Chemistry. The C-terminus of the chain is attached to an insoluble polymer bead, and the chain grows toward the N-terminus. Every residue takes one cycle of deprotection, coupling with an activated amino acid whose side chain is protected, and washing — and since the growing chain is fixed to the bead, surplus reagents are simply washed off instead of being removed by chromatography.
Coupling efficiency and purity
How efficiently each coupling works limits the purity that can be reached, and the numbers are harsh. With 99% per step, a 30-residue peptide gives roughly 74% full-length product; with 98%, just 55%. The rest consists of deletion and truncation sequences that have to be stripped out by preparative HPLC — which is why longer peptides cost disproportionately more per milligram and why, beyond about 50 residues, chemical synthesis yields to recombinant production.
Current practice relies on Fmoc chemistry, piperidine for deprotection and trifluoroacetic acid for cleavage, which is why peptides are obtained as a TFA salt unless the counter-ion is exchanged. Difficult sequences with stretches prone to aggregation lower the efficiency further. See synthetic peptides and HPLC purity explained.
Related terms
protecting group · purity · peptide bond