PE-22-28 is a seven-residue peptide with the sequence Gly-Val-Ser-Trp-Gly-Leu-Arg, the shortened active fragment of spadin and a selective blocker of the TREK-1 two-pore domain potassium channel. Reported potency in the sub-nanomolar range makes it more active than the parent spadin sequence, and it is used in electrophysiology and neuronal culture work on TREK-1. NuVion supplies PE-22-28 as a laboratory chemical for in vitro research use only.
Key facts
| Type | Synthetic heptapeptide, spadin fragment |
| Amino acid count | 7 |
| Sequence | H-Gly-Val-Ser-Trp-Gly-Leu-Arg-OH |
| Parent peptide | Spadin, residues 22 to 28 |
| Parent protein | Sortilin propeptide |
| Molecular target | TREK-1 (KCNK2) two-pore domain potassium channel |
| Reported potency | IC50 in the sub-nanomolar range |
| Supplied form | Lyophilised powder in a sealed vial |
Structure and chemistry
PE-22-28 comes from an unusual biological source. Sortilin is synthesised with an N-terminal propeptide that is cleaved during maturation, and that released propeptide fragment is spadin, a 17-residue peptide. Systematic truncation of spadin identified residues 22 to 28 as the minimal segment retaining activity at TREK-1, and that heptapeptide is PE-22-28. The naming reflects the position of the fragment within the propeptide numbering.
The sequence is compact and amphipathic. Glycine at positions one and five gives backbone flexibility, valine and leucine supply hydrophobic surface, the tryptophan at position four is the single aromatic residue, the serine offers a hydrogen bonding hydroxyl, and the C-terminal arginine carries a positive charge. The combination of an aromatic residue flanked by small flexible residues and a terminal basic residue is characteristic of peptides that interact with the extracellular face of ion channels, where the aromatic side chain typically anchors into a hydrophobic pocket while the charged residue makes an electrostatic contact.
The tryptophan governs both detection and stability. It provides absorbance at 280 nm and fluorescence near 350 nm for HPLC detection and for direct concentration measurement, and it is the residue most susceptible to oxidation and photodegradation, so solutions are kept out of the light. With free termini the peptide is open to both amino and carboxypeptidase attack, so it is short-lived in serum-containing medium. Analogues in which the termini are capped, or the tryptophan replaced with a non-oxidisable aromatic, appear in the structure-activity literature. Purity is determined by RP-HPLC and identity by mass spectrometry.
Mechanism of action
TREK-1, encoded by KCNK2, is a two-pore domain potassium channel that produces a background leak current setting the resting membrane potential of many neurons. It is opened by membrane stretch, by intracellular acidification, by warming and by polyunsaturated fatty acids such as arachidonic acid, which makes it a polymodal sensor. Because it is a leak channel, its activity is inhibitory in effect: open TREK-1 holds the membrane hyperpolarised and raises the threshold for firing.
PE-22-28 blocks the channel. The block is described as acting from the extracellular side and as selective for TREK-1 over the related two-pore channels TRAAK and TREK-2 and over the classical voltage-gated potassium currents, which is the property that makes it useful as a pharmacological tool. Closing the leak conductance depolarises the resting membrane potential and increases excitability, and this is the primary readout in patch clamp experiments. Downstream cellular work in neuronal and neural progenitor culture has followed changes in proliferation and differentiation markers and in the phosphorylation state of signalling proteins that respond to altered excitability. Because the potency is sub-nanomolar, careful attention to adsorption losses and to accurate low-concentration dilution series is a practical requirement of using it well.
Research applications
- Whole-cell and single-channel patch clamp on TREK-1 expressing cell lines, measuring block of the background potassium current.
- Selectivity profiling against TREK-2, TRAAK and other potassium conductances under matched recording conditions.
- Resting membrane potential and excitability measurement in primary neuronal culture.
- Mechanosensitivity and pH sensitivity experiments, testing whether block persists across the channel’s activating stimuli.
- Neural progenitor proliferation and differentiation assays with BrdU or EdU incorporation and lineage marker staining.
- Structure-activity comparison against full-length spadin and truncated or capped analogues.
PE-22-28 sits in NuVion’s Neuroscience category with the other neuroactive research peptides.
Handling in the laboratory
PE-22-28 is supplied lyophilised and is reconstituted with bacteriostatic water added slowly down the side of the vial and swirled gently until dissolved. The heptapeptide is water-soluble. The reconstitution calculator converts vial content and diluent volume into a stock concentration, and the tryptophan allows the result to be cross-checked by absorbance at 280 nm. Because working concentrations are sub-nanomolar, serial dilutions are prepared in low-binding tubes with a carrier protein where the assay permits, since adsorption to plastic at these concentrations can account for a large fraction of the nominal amount.
Light protection matters because of the tryptophan, so stock and working solutions are kept dark and amber tubes are used where possible. Unopened vials are kept sealed, dry, protected from light and refrigerated as stated on the product documentation. Reconstituted solution is refrigerated, kept in the dark and used within the period given there, or aliquoted into single-use volumes and frozen. Given the short peptidase half-life in serum-containing medium, perfusion or acute application is more common than prolonged incubation in electrophysiology work.
Testing and supply from NuVion
NuVion’s PE-22-28 is manufactured at a GMP-audited facility and independently tested by Janoshik Analytical, with purity determined by RP-HPLC and identity confirmed by mass spectrometry. The Certificate of Analysis for a tested batch is published on the product page and in the COA library. The peptide is supplied lyophilised in sealed vials and dispatched from within Australia.
Related compounds
Other neuroactive peptides used in comparable culture and recording work include Selank, Semax and DSIP.
Frequently asked questions
What is PE-22-28 used for in research?
It is used as a selective pharmacological blocker of TREK-1 in patch clamp electrophysiology, in resting membrane potential and excitability measurement on neuronal culture, and in neural progenitor proliferation and differentiation assays where TREK-1 activity is the variable under test.
How does PE-22-28 relate to spadin?
Spadin is the 17-residue propeptide fragment released during sortilin maturation. Truncation studies narrowed the active region to residues 22 to 28, and that heptapeptide is PE-22-28, with reported potency at TREK-1 greater than the full-length parent.
Is PE-22-28 a therapeutic good in Australia?
No. NuVion’s PE-22-28 is a laboratory chemical for in vitro research. It is not included in the Australian Register of Therapeutic Goods, has not been assessed by the Therapeutic Goods Administration, and is not for human or veterinary use.
How should PE-22-28 be stored?
Lyophilised vials are kept sealed, dry, protected from light and refrigerated per the product documentation. Reconstituted solution is refrigerated, kept dark and used within the stated period, or aliquoted and frozen. Low-binding tubes are used for the sub-nanomolar dilution series.
Research use only. This product is a laboratory chemical supplied for in vitro research. It is not included in the Australian Register of Therapeutic Goods and has not been assessed by the Therapeutic Goods Administration for quality, safety or efficacy. It is not for human or veterinary use, and nothing on this page is a representation about therapeutic use.
