PE-22-28 is a seven-residue peptide cut from the C-terminal end of spadin, and spadin is itself a fragment of the propeptide that is removed when the receptor sortilin matures. It is studied because it blocks TREK-1, a two-pore-domain potassium channel whose deletion produces a depression-resistant phenotype in mice. The name is a set of coordinates: PE for the propeptide, 22-28 for the residues kept. This post explains the lineage, what the channel is, why the fragment was shortened, how to handle a 774-dalton peptide, and what the current certificate for the PE-22-28 in the catalogue reports.
Where does the name come from?
Sortilin is a receptor made as a precursor, and a 44-residue propeptide (PE) is cleaved from it during maturation. Spadin is the name given to residues 12 to 28 of that propeptide, a 17-residue sequence found to bind TREK-1 and block it. Djillani and colleagues then asked how much of spadin was needed, and found that the last seven residues, positions 22 to 28, retained the channel inhibition with better stability. That fragment is PE-22-28.
| Name | What it is | Length |
|---|---|---|
| Sortilin | A membrane receptor of the VPS10P family | A large single-pass membrane protein |
| PE (propeptide) | The N-terminal segment removed during sortilin maturation | 44 residues |
| Spadin | Residues 12 to 28 of PE | 17 residues |
| PE-22-28 | Residues 22 to 28 of PE | 7 residues |
The five-names post covers why a research code like this one is more reliable than a trade name: the numbers point at a defined stretch of a defined sequence, and the certificate's mass either matches it or does not.
What is TREK-1, and why block it?
TREK-1, gene name KCNK2, is a two-pore-domain potassium channel. Channels in this family set the resting membrane potential of the cells that express them by leaking potassium outward; they are opened by mechanical stretch, by some lipids and by volatile anaesthetics. Mice in which the gene is deleted behave, in standard behavioural assays, like mice treated with antidepressant drugs, and several such drugs inhibit the channel. That is the reason a blocker is interesting, and it is a reason about a channel in a model, not a claim about a compound in a person. The trial-data post explains why the distinction is worth keeping.
In a laboratory, TREK-1 blockade is measured directly: patch-clamp recording of cells expressing the channel, with and without the peptide, is the assay Djillani's group used, and it is the assay in which PE-22-28's effect was characterised. The receptor table lists TREK-1 as this compound's target alongside the receptors of the other neuro-class peptides.
Why shorten spadin to seven residues?
Three reasons appear in the 2017 paper.
Stability. Shorter peptides with fewer cleavage sites last longer in the systems the authors tested. The half-life post covers why length and sequence set a peptide's lifetime.
Potency. The shortened analogues inhibited TREK-1 at lower concentrations than spadin in their recordings.
Cost and consistency. A seven-residue solid-phase synthesis is simpler than a seventeen-residue one, with fewer opportunities for deletion sequences, which the synthesis post explains.
How does a 774-dalton peptide behave at the bench?
Like Selank and Semax, which are the same size class. It dissolves readily in water or reconstitution solution, does not need a carrier protein at ordinary working concentrations, and tolerates freezing well. Ten milligrams is 12.9 µmol; in 1 mL that is a 12.9 mM stock, and a 1 µM working solution for a patch-clamp bath is a 1 in 12,900 dilution. The concentration table gives the syringe arithmetic for the 10 mg vial, and the aliquoting rules apply as for any short peptide.
One handling note specific to electrophysiology: peptides in a recording bath can adsorb to the tubing of a perfusion system. Pre-conditioning the line with the working solution, or adding a small amount of albumin to the bath if the protocol allows, keeps the concentration at the cell close to the nominal one.
What does the current certificate report?
Lot PE2228-0528, certificate COA4859, was issued by Bioviridian Inc. on 17 June 2026 against a 10 mg sample of white lyophilized powder. The PDF is published unaltered on the certificate page.
| Certificate line | Result | What it tells you |
|---|---|---|
| Identity, MALDI-MS | PE-22-28, observed mass 773.9 | Matches the seven-residue fragment, not the 17-residue spadin |
| Content, HPLC quantitation | 10.21 mg | Slight overage against the 10 mg label |
| Purity, RP-HPLC at 214 nm | 99.9% | One dominant peak; see the chromatogram post |
| Endotoxin | < 0.05 EU/mL | Suitable for cell work without correction |
| Heavy metals | Conforms | Included on the June 2026 certificate layout |
| Sterility | Conforms | Included on the June 2026 layout; see the sterility post for what the three tests each mean |
The identity line is the one that matters most for this compound, because spadin and PE-22-28 are sold under overlapping names and differ by ten residues. A mass of 773.9 is the short fragment; the full spadin would be well over 1,900.
How does it compare with the other neuro-class peptides in the catalogue?
| Compound | Target | Residues | Mass |
|---|---|---|---|
| PE-22-28 | TREK-1 channel (blocker) | 7 | 773.9 |
| Selank | Studied for GABAergic and immune signalling | 7 | 751.9 |
| Semax | Studied for BDNF and trkB expression | 7 | 813.9 |
| P-21 | CNTF-derived; studied in neurogenesis models | Short, adamantane-containing | 578.6 observed |
| Dihexa | Studied at the HGF/c-Met system | 6 | 501.7 |
PE-22-28 is the only one of the five whose target is an ion channel rather than a receptor or a growth-factor system, which decides the assay: electrophysiology rather than a binding or expression readout.
Frequently asked questions
Is PE-22-28 the same as spadin?
No. Spadin is 17 residues; PE-22-28 is the last seven of them. The certificate's mass, 773.9, identifies the short fragment.
Does the catalogue stock spadin itself?
No. PE-22-28 is the spadin-derived compound supplied, as a 10 mg lyophilized powder for laboratory research use only.
What assay demonstrates TREK-1 blockade?
Patch-clamp recording of TREK-1 currents in a cell line expressing the channel, before and after applying the peptide. That is the method in the primary literature, and a binding assay alone does not show block.
Why does the certificate include sterility when the August certificates do not?
The certificate layouts differ by issue date. The June 2026 layout reports sterility and heavy metals; the August 2026 layout reports heavy metals only. Both report identity, content, purity and endotoxin, which are the lines that apply to every use.
How should the methods section describe it?
"PE-22-28 (spadin residues 22 to 28)", the supplier, lot PE2228-0528, certificate COA4859, the observed mass, and the stock concentration in molar terms. The methods-section post has the template.
References
- Djillani A, Pietri M, Moreno S, et al. Shortened spadin analogs display better TREK-1 inhibition, in vivo stability and antidepressant activity. Frontiers in Pharmacology 2017;8:643. doi.org/10.3389/fphar.2017.00643
- PubChem, National Library of Medicine. PE 22-28, CID 165437303, C35H55N11O9, 773.9 g/mol. Read 27 September 2026. pubchem.ncbi.nlm.nih.gov/compound/165437303
- Bioviridian Inc. Certificate of analysis COA4859, PE-22-28 10 mg, lot PE2228-0528, issued 17 June 2026. coa.html
Every product mentioned is sold for laboratory research use only and is not for human or animal use. Nothing on this page describes or recommends use of the material sold here in humans or animals.
