PE-22-28 Research Peptide

PE-22-28 is a synthetic research peptide made of seven amino acids, Gly-Val-Ser-Trp-Gly-Leu-Arg. It was designed in 2017 as a shorter, more stable version of spadin, a peptide taken from the sortilin propeptide. It is used in laboratory research on the TREK-1 potassium channel, in cell-based channel recordings and in rodent behavioural, neurogenesis and ischaemia models.

“PE” is the name of the 44-amino-acid propeptide cut from sortilin as it matures, and “22-28” gives the positions of the residues taken from it. So PE-22-28 is simply residues 22 to 28 of that propeptide. Spadin, by comparison, is residues 12 to 28, which is why the two peptides share the same final seven amino acids.

It is the last seven residues of spadin’s seventeen, so it is literally a miniature spadin. The researchers found it by studying the fragments spadin leaves behind when it breaks down in blood. In their tests the shortened version blocked TREK-1 at a much lower concentration than spadin and kept its effect in mice for many more hours, so the shorter name stuck in later papers.

TREK-1 is a potassium channel in the outer membrane of nerve cells, also known as K2P2.1, with its gene called KCNK2. It lets potassium leak out of the cell, which keeps the cell’s electrical charge low and makes it harder to fire. Research interest grew after mice lacking the TREK-1 gene were found to behave much like animals already given mood-related compounds, which pointed to the channel as a research target.

Spadin worked well in the original studies, but its effect in mice faded within about seven hours and it was broken down in serum within half an hour. The group tried reversing the backbone chemistry, joining the chain into a ring and shortening it. Shortening gave the most potent, longest-lasting result, and PE-22-28 was the outcome of that work.

In the 2017 study it was tested against TREK-1’s close relatives. It had no measurable effect on TREK-2, TRAAK, TRESK or TASK-1, and it did not change the cardiac hERG current even at 10 micromolar, far above the concentration needed to block TREK-1. That selectivity is one reason it is useful as a laboratory tool for studying TREK-1 on its own.

All three are short peptides used in neurocognitive research, but they come from different sources. Semax is based on a fragment of the hormone ACTH, and Selank on the immune peptide tuftsin. PE-22-28 comes from the sortilin propeptide and is studied mainly through one defined target, the TREK-1 potassium channel, which makes its mechanism unusually specific.

The hippocampus is one of the few brain regions where new neurons keep forming in adult animals, and the rate is a widely used marker in mood research. Researchers label dividing cells with a tracer called BrdU and count them. In the 2017 study, PE-22-28 roughly doubled that count after just four days, a timescale that interested the group because conventional reference compounds usually take several weeks.

Mice were given mini-spadin after a blockage of the middle cerebral artery. Because low concentrations increased TREK-1 activity and higher ones blocked it, a low dose was used in the first week and a higher dose later. The researchers reported less loss of dopamine-producing cells, better motor and memory scores, more new neurons and synapses, and normal behaviour in mood-related tests.

Yes. TREK-1 is also present in insulin-secreting cells of the pancreas. A 2021 study found that mini-spadin raised calcium inside these cells, protected them against cell death triggered by the inflammatory signal interleukin-1-beta through the CREB pathway, and encouraged them to divide. It was active at 10 nanomolar, a tenth of the concentration spadin needed in the same experiments.

Very similar peptides can look alike on HPLC. The 2017 study found that PE 22-27, missing only the final arginine, lost its activity, and swapping the first glycine for alanine creates a different analogue just 14 mass units heavier. Mass spectrometry confirms the full GVSWGLR chain at about 773.9 daltons, so researchers know they have the exact sequence described in the published work.

PE-22-28 is not a controlled drug under the Misuse of Drugs Act 1971, and it is not a licensed medicine in the UK. It is sold in the UK as a research compound for laboratory use only, which is how Crown Peptides supplies it. This is general information, not legal advice.

PE-22-28 is coming soon to Crown Peptides in 10mg vials, available singly or in packs of 3, 5 or 10 with a saving on every vial. Orders ship from the UK, and every batch is independently tested, with its Certificate of Analysis published on this page once stock arrives.

Ten milligrams of a 774-dalton peptide is roughly 13 micromoles. The published cell work used PE-22-28 at nanomolar concentrations, so one vial covers a substantial amount of in vitro work. The 5 and 10-vial packs keep a longer project on a single batch, which makes results easier to compare from start to finish.

Keep the unreconstituted powder at -20°C ± 5°C, dry and away from light. The sequence contains tryptophan, an amino acid that is sensitive to light and oxidation, so vials are best kept sealed and dark until use. Prepared solutions should follow storage conditions validated for your study design, and each batch’s Certificate of Analysis documents the material as dispatched.