How peptides are made

Solid-phase synthesis

The method is called solid-phase peptide synthesis. It was introduced by the chemist Bruce Merrifield in 1963 and earned him the Nobel Prize in Chemistry in 1984. The idea is to anchor the first amino acid to a tiny solid bead, called a resin, and build the chain outwards from it.

The cycle

1. The first amino acid is attached to the resin.
2. A protective group on its free end is removed, which exposes the spot where the next amino acid will join.
3. The next amino acid, which carries its own protective group, is added and bonds to the chain.
4. The beads are washed so that anything that did not react is rinsed away.
5. The cycle repeats, one amino acid at a time, until the chain is complete.

Releasing the peptide

When the last amino acid is in place, the finished chain is cut from the resin and the remaining protective groups are removed. The result is a mixture, and the target peptide is then separated out, normally by chromatography, a technique that sorts molecules by how they move through a column.

Why length matters

Every cycle has to work almost perfectly, and small losses add up over a long chain. That is why shorter peptides are easier to make this way and very long ones are often produced by other methods.

From solution to powder

The purified peptide is dissolved in water and then freeze-dried, which leaves it as a stable powder that can be sealed into vials. Our post on lyophilized peptides explains that last step.

Words you will meet

• Resin: the tiny bead the chain is built on.
• Protective group: a temporary cap on a reactive end of an amino acid, removed at the right moment.
• Chromatography: sorting molecules by how they travel through a column.
• Mass spectrometry: weighing molecules, which is one way to confirm a peptide is the size that was intended.

Research use only

Pep Pantry products are sold for laboratory research by adults. They are not for human or veterinary use. This article describes the chemistry for laboratory readers only.