Solid-phase peptide synthesis (SPPS)

Last updated: 2026-10-10 · Research use only. Not for human or veterinary use.

Short answer

Solid-phase peptide synthesis (SPPS) builds a peptide one amino acid at a time on an insoluble resin, from the C-terminus to the N-terminus. In Fmoc chemistry each residue is coupled, its Fmoc protecting group removed with base, and the chain finally cleaved from the resin with trifluoroacetic acid. [1]

At a glance

Term	Definition / specification
Direction	C-terminus → N-terminus
Common chemistry	Fmoc/tBu
Deprotection	Piperidine in DMF (removes Fmoc)
Final cleavage	TFA with scavengers
Typical impurities	Deletion and truncated sequences, aspartimide products, racemised residues
Purification	Preparative RP-HPLC, then lyophilisation

Where impurities arise

Incomplete couplings leave deletion sequences; side reactions such as aspartimide formation at Asp-Gly motifs create related species that HPLC must resolve.

Why TFA appears later

The cleavage acid stays associated with basic groups, which is why peptides are often delivered as trifluoroacetate salts.

FAQ

Why build from the C-terminus?

The C-terminal residue is anchored to the resin, leaving the N-terminal amine free for the next coupling.

What is a deletion sequence?

A chain missing one residue because a coupling step did not go to completion.

Related reference pages

Sources

Hansen PR et al. Fmoc Solid-Phase Peptide Synthesis. Methods Mol Biol. 2015. PMID: 26424261
Behrendt R et al. Advances in Fmoc solid-phase peptide synthesis. J Pept Sci. 2016. PMID: 26785684 · PMC4745034
Kong MJW et al. Aspartimide Formation and Its Prevention in Fmoc Chemistry Solid Phase Peptide Synthesis. Chembiochem. 2025. PMID: 40857621 · PMC12447389
PubChem. Trifluoroacetic acid (C2HF3O2, 114.02 g/mol). CID 6422

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Plain

Sable Peptides. (2026). solid-phase-peptide-synthesis. UK Research Peptide Reference. Retrieved 11 October 2026, from https://www.sablepeptides.co.uk/ref/solid-phase-peptide-synthesis

APA

Sable Peptides. (2026, October 11). *solid-phase-peptide-synthesis*. UK Research Peptide Reference. https://www.sablepeptides.co.uk/ref/solid-phase-peptide-synthesis

BibTeX

@misc{sable_solid-phase-peptide-synthesis_2026,
  author = {{Sable Peptides}},
  title = {{solid-phase-peptide-synthesis}},
  year = {2026},
  howpublished = {\url{https://www.sablepeptides.co.uk/ref/solid-phase-peptide-synthesis}},
  note = {Accessed 11 October 2026. CC BY 4.0}
}

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Date modified: 2026-10-16