Encyclopedia entry

Solid-phase peptide synthesis (SPPS)

Solid-phase peptide synthesis is the standard manufacturing method for research peptides and many medicines. Bruce Merrifield published the method in 1963 and won the 1984 Nobel Prize in Chemistry for it. Amino acids are added one at a time to a growing chain anchored to an insoluble resin, with chemical wash steps between additions to remove unreacted material.

How the chain grows

• · First amino acid attached to the solid resin (typically polystyrene-based).
• · N-terminus protecting group removed by acid or base wash.
• · Next protected amino acid coupled to the exposed terminus.
• · Cycle repeats: wash, deprotect, couple, wash, deprotect, couple.
• · Final cleavage releases the peptide from the resin and removes side-chain protecting groups.
• · HPLC purification separates the target peptide from incomplete sequences and side-products.

Why cost scales non-linearly

Each cycle has an efficiency rate, typically 99%+. At 99% per cycle, a 30-amino-acid peptide retains only about 74% of the full-length product after synthesis (0.99 to the power 30). The shorter the peptide, the higher the yield, the lower the cost per gram. A 5-amino-acid peptide is dramatically cheaper per gram than a 44-amino-acid peptide. This is why Tesamorelin (44 aa) costs 2 to 3 times Sermorelin (29 aa) per equivalent quantity, and Ipamorelin (5 aa) is one of the cheapest.

Why purification matters

The HPLC purification step is where retailer-grade purity is determined. A 99%+ HPLC purity claim on a 30-amino-acid peptide means the retailer is purifying away the truncated sequences that the synthesis process inevitably produces. This is why the per-gram cost of a high-purity 30+ amino acid research peptide is substantially higher than the per-gram cost of a short peptide.

Related: HPLC purity · research peptides hub.