PE-22-28

PE-22-28 is a synthetic heptapeptide, Gly-Val-Ser-Trp-Gly-Leu-Arg, matching residues 22 to 28 of the 44-residue propeptide released when sortilin, also catalogued as neurotensin receptor 3, is processed. Its formula is C35H55N11O9, its molecular weight 773.9 g/mol, its CAS number 1801959-12-5 and its PubChem CID 165437303. The chain has no cysteine and no disulfide bond, its single tryptophan is the only aromatic residue, and the C-terminal arginine makes it basic. It is characterised in the literature as a blocker of TREK-1, the two-pore-domain potassium channel encoded by KCNK2.

The compound is a shortened derivative of spadin, and that relationship is the point of it. Spadin is the 17-residue fragment PE 12-28 of the same propeptide, sequence Ala-Pro-Leu-Pro-Arg-Trp-Ser-Gly-Pro-Ile-Gly-Val-Ser-Trp-Gly-Leu-Arg, so PE-22-28 is its last seven residues, identified among spadin’s breakdown products in blood and made synthetically. Reported patch-clamp work on a human TREK-1 cell line gave a half-maximal inhibitory concentration of 0.12 nM for PE-22-28 against 40 to 60 nM for spadin. Material is supplied as lyophilized (freeze-dried) powder for laboratory research use only.

The lineage starts with sortilin, whose maturation releases the propeptide this fragment comes from. Mazella and colleagues at the CNRS institute in Valbonne described spadin in 2010 as a sortilin-derived peptide acting on rodent TREK-1 channels (PubMed 20405001). Its limitation was short persistence in vivo, which the shorter analogues answer.

PE-22-28 was reported by Djillani and colleagues in 2017, from spadin blood degradation products, characterised by patch clamp on a human TREK-1 cell line and in rodent assays (PubMed 28955242). The group reviewed the programme in 2019 (PubMed 30291907), and Pietri and colleagues studied sortilin-derived peptides in a rodent stroke model (PubMed 31325429).

The evidence base is preclinical, narrow and dominated by one originating laboratory. Work naming PE-22-28 runs to a handful of papers; the wider TREK-1 and spadin literature describes the parent or the channel, not this fragment. No human trial is published or registered, and nothing here describes a human outcome. Every reference below was checked against PubMed retraction records; none carries a retraction or concern notice.

The mechanism reported for PE-22-28 is blockade of TREK-1, a two-pore-domain potassium channel carrying a background, or leak, current. Such channels are open across a wide voltage range and help set the resting membrane potential, so inhibiting one reduces potassium efflux and depolarises the cell. In the originating study it inhibited human TREK-1 currents in transfected cells more potently and selectively than spadin, and altering either terminus changed whether blocking was kept (PubMed 28955242).

Two distinctions are useful. The first is against spadin: same target, different length and potency, so the two are not interchangeable in a study design. The second is against assuming a TREK-1 blocker is by definition a neuroscience reagent. KCNK2 is expressed well beyond neurons, in chondrocytes, macrophages and vascular tissue, and TREK-1 forms heterodimers with TREK-2 and TWIK-1 that change the current measured.

A methodology caveat runs through the record. Potency figures come from patch clamp in a transfected cell line, the in vivo findings from rodent paradigms with small groups, so every result belongs to its assay.

Sealed lyophilized PE-22-28 is stored at -20°C, shielded from light, in the unopened container. No duration is asserted here: the stability window for a batch is on its Certificate of Analysis.

Lyophilized material is hygroscopic, meaning it takes up atmospheric moisture, so a container reaches ambient temperature before opening. Freeze-thaw cycling is avoided. Tryptophan is the oxidation- and light-sensitive residue, the reason to keep the vial dark as well as cold.

Reconstitution is the term for returning a lyophilized compound to solution; this page defines it and gives no procedure. PE-22-28 is of mixed character, a basic arginine and polar serine against a hydrophobic core, and sits in the aqueous solubility class.

Solid material is handled in low humidity with minimal open-container exposure. Short peptides adsorb to glass and plastic at low concentration, which matters for a compound active at sub-nanomolar levels. Preparation parameters belong to the cited methodology and lot COA.

Identity and purity here are established by reverse-phase high-performance liquid chromatography and mass spectrometry, the primary check being a mass consistent with 773.9 g/mol. Verified purity is documented per lot on the COA.

Three checks are specific here. Tryptophan oxidation adds 16 mass units and shows as a separate chromatographic peak. Terminal form matters more than usual, since the originating study reported that changing either end altered blocking, so a free acid lot is confirmed rather than assumed. Counter-ion content and residual water set fill weight against net peptide, recorded on the COA.

PE-22-28 is catalogued with short peptides studied in receptor-biology models.

• DSIP.
  A natural nonapeptide with no cloned receptor, the opposite of a named channel target.
• Semax.
  A synthetic ACTH(4-10) analogue studied in rodent neuro models.
• P21.
  A CNTF-derived peptidomimetic, another fragment cut from a larger parent.
• N-Acetyl Semax.
  Terminal capping used to extend a short peptide’s stability.

Mazella J, Petrault O, Lucas G, et al. (2010). Spadin, a sortilin-derived peptide targeting rodent TREK-1 channels. PLoS Biol.
PubMed 20405001

Djillani A, Pietri M, Moreno S, et al. (2017). Shortened spadin analogs display better TREK-1 inhibition and in vivo stability. Front Pharmacol.
PubMed 28955242

Djillani A, Pietri M, Mazella J, et al. (2019). TREK-1 blockers: a focus on spadin. Pharmacol Ther.
PubMed 30291907

Pietri M, Djillani A, Mazella J, et al. (2019). Protective effects on stroke recovery induced by sortilin-derived peptides. Neuropharmacology.
PubMed 31325429

Peptides.com lists one PE-22-28 research product, a sealed lyophilized vial from Real Peptides at an 8mg fill. That per-vial strength is a product specification, not a research quantity. Vials are the only format listed. PE-22-28 is new to the catalogue with no chemical information page, so the identity figures above come from PubChem. Each lot ships with a published COA.

• Browse all PE-22-28 research products

• Real Peptides PE-22-28, 8mg lyophilized vial

These products are sold for Research Use Only and are not intended for human consumption.