Building a Peptide One Residue at a Time

The trick is to anchor the start

In the 1960s Bruce Merrifield had an idea: attach the first residue to an insoluble resin bead. Now every excess reagent can be washed away by filtering, and the growing chain stays put. His 1963 paper built a four-residue chain this way, and the method earned him the 1984 Nobel Prize in Chemistry.

One cycle repeated

1. Deprotect the end of the chain by removing a temporary cap.
2. Wash the bead.
3. Couple the next residue, which arrives with its own protective caps.
4. Wash again.

Repeat for each letter in the sequence, working from the C-terminus toward the N-terminus.

Why yields fall with length

Even a 99 percent efficient step leaves losses. After 30 cycles only about three quarters of chains are fully correct, and the leftovers are near-identical impostors that are hard to separate.

Finishing

The chain is cleaved off the resin, and HPLC (high-performance liquid chromatography) separates the target from failures. Mass spectrometry then confirms the weight matches the sequence.

Why it matters to buyers

Purity and identity are properties of a specific batch. They are verified by analysis, not by a claim on a website.