The method, developed by Bruce Merrifield (Nobel Prize in Chemistry, 1984), anchors the first amino acid to small resin particles. From there a cycle is repeated: the protecting group on the free end is removed, the next amino acid is coupled and excess reagents are washed away. The chemistry most used today protects amino groups with Fmoc.
When the chain is complete, an acid treatment, usually with trifluoroacetic acid (TFA), releases the peptide from the resin and removes the protecting groups from the side chains. The crude product is purified by preparative HPLC and freeze-dried.
Each cycle has a high but not perfect yield. If a coupling fails on some molecules, those chains end up one amino acid short: these are deletion sequences, the most typical synthesis impurity and the reason purification is essential.
The synthetic origin explains which impurities to look for (deletions, truncations, leftover protecting groups) and why almost all peptides arrive as a TFA or acetate salt. The certificate of analysis summarises how much of all that was removed.
Related terms
Learn it in depth at the Peptide University
- Classification and solid-phase synthesis · Module 1
- Related impurities and counterions · Module 7
Definition for educational and scientific purposes. It is not medical advice or a recommendation for use. NeoPeptidos products are sold labelled for research use only (RUO).