---
title: "Solid-phase peptide synthesis (SPPS) | Sable Peptides"
description: "How research peptides are built residue by residue on a resin using Fmoc chemistry, and where impurities come from."
canonical: https://www.sablepeptides.co.uk/ref/solid-phase-peptide-synthesis
publisher: Sable Peptides Limited (UK company 17488610)
note: Research use only. Not for human or veterinary use.
---

# Solid-phase peptide synthesis (SPPS)

## 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

-   [TFA vs acetate salts of peptides](/ref/tfa-vs-acetate-salts)
-   [What HPLC purity means for a research peptide](/ref/hplc-purity)
-   [C-terminal amidation and N-terminal acetylation](/ref/terminal-modifications)
-   [Reference index](/ref)

## Sources

1.  Hansen PR et al. Fmoc Solid-Phase Peptide Synthesis. *Methods Mol Biol*. 2015. PMID: [26424261](https://pubmed.ncbi.nlm.nih.gov/26424261/)
2.  Behrendt R et al. Advances in Fmoc solid-phase peptide synthesis. *J Pept Sci*. 2016. PMID: [26785684](https://pubmed.ncbi.nlm.nih.gov/26785684/) · [PMC4745034](https://pmc.ncbi.nlm.nih.gov/articles/PMC4745034/)
3.  Kong MJW et al. Aspartimide Formation and Its Prevention in Fmoc Chemistry Solid Phase Peptide Synthesis. *Chembiochem*. 2025. PMID: [40857621](https://pubmed.ncbi.nlm.nih.gov/40857621/) · [PMC12447389](https://pmc.ncbi.nlm.nih.gov/articles/PMC12447389/)
4.  PubChem. Trifluoroacetic acid (C2HF3O2, 114.02 g/mol). CID [6422](https://pubchem.ncbi.nlm.nih.gov/compound/6422)

\---

Research use only. This page describes laboratory chemistry and analytical methods. It is not advice on any use in people or animals.

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Research use only. Not for human or veterinary use.

## Cite this

Research use only. Not for consumption. No health claims.

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

Reviewed by Sable Peptides editorial team · 14 October 2026 · [Editorial policy](/editorial-policy)