How are peptides made?

In the lab, peptides are built one amino acid at a time on a tiny bead. In the body, cells read them from DNA.

In the lab: solid-phase peptide synthesis

1. Anchor. The first amino acid is attached to a tiny resin bead.
2. Protect. Each new amino acid has a temporary chemical "cap" on its amino end, so it only joins at the right spot.
3. Couple. The next amino acid is added and forms a peptide bond with the chain.
4. Wash. Leftover chemicals are rinsed away. Because the chain is stuck to the bead, nothing is lost.
5. Deprotect. The cap is removed, ready for the next amino acid.
6. Repeat the cycle until the full sequence is built.
7. Cleave and purify. The finished peptide is cut free from the bead, purified (usually by HPLC) and freeze-dried into a powder.

Why the bead matters

Before the bead method, every step needed the product to be separated and purified by hand, so a long peptide could take years. In 1959, Bruce Merrifield wrote in his notebook that there was "a need for a rapid, quantitative, automatic method for the synthesis of long chain peptides." Anchoring the chain to a solid support cut the time from years to days, and it won him the 1984 Nobel Prize in Chemistry.

Accuracy at every step matters enormously. The Nobel committee's example: raising each step's yield to 99.5% lifted the overall yield of a long synthesis from 0.003% to 61%.

In the body

Cells make peptides and proteins by reading genes. The DNA code is copied into messenger RNA, and ribosomes read it three letters at a time, adding the matching amino acid to a growing chain. Many peptide hormones are first made as a longer precursor chain, which enzymes then cut down to size.