Almost every synthetic research peptide available today is made using solid-phase peptide synthesis (SPPS), a method developed in the 1960s that remains the industry standard. Understanding the broad strokes of how it works makes the purity and identity figures on a CoA easier to interpret — they're a direct readout of how cleanly this specific process ran.
Building a chain one residue at a time
SPPS works by anchoring the first amino acid to a solid resin bead, then adding the sequence's remaining amino acids one at a time in the correct order, working from one end of the chain to the other. Each addition is called a coupling step.
Because the growing chain stays attached to an insoluble resin throughout, excess reagents and by-products from each step can simply be washed away, rather than needing to be separated from a chain still in solution — that's the practical advantage the 'solid phase' gives the process.
Coupling and deprotection cycles
Each amino acid added carries a temporary protecting group on its reactive end, so it can only join the chain at the intended point rather than reacting with itself or other exposed groups. A deprotection step removes that group before the next amino acid is coupled on, and the cycle repeats until the full sequence is assembled.
- Couple the next protected amino acid onto the resin-bound chain.
- Wash away excess unreacted reagent.
- Deprotect the newly added residue's reactive end.
- Wash again, then repeat for the next amino acid in the sequence.
Why purification still follows synthesis
No coupling cycle runs at 100% efficiency across every single step, so a finished synthesis is a mixture — mostly the target sequence, plus a smaller fraction of truncated or otherwise imperfect chains from steps that didn't go to completion. Cleaving the chain off the resin and purifying it (typically by preparative HPLC) is what separates the intended product from those by-products.
That purification step is exactly what a CoA's purity figure is reporting on — how effectively the target sequence was isolated from the synthesis by-products that are an inherent part of the process, not a manufacturing error.