PE-22-28

PE-22-28 is a seven-residue peptide, Gly-Val-Ser-Trp-Gly-Leu-Arg, designed from the blood degradation products of spadin, a 17-amino-acid peptide derived from the propeptide of the neurotensin receptor 3 (NTSR3/sortilin). Like spadin, the PE-22-28 peptide blocks the two-pore domain potassium channel TREK-1, and researchers have compared its channel affinity, duration of action and effects on neurogenesis and synaptogenesis in mice with those of the parent peptide. Research Market supplies PE-22-28 as a lyophilized research reagent, with purity and identity data for each lot reported on its certificate of analysis. It is sold strictly for laboratory research use.

Chemical structure and identification

• Molecular formula: C₃₅H₅₅N₁₁O₉
• Molecular weight: 773.9 g/mol
• CAS number: 1801959-12-5
• PubChem CID: 165437303
• Amino acid sequence: Gly-Val-Ser-Trp-Gly-Leu-Arg (GVSWGLR)
• Synonyms: PE 22-28
• Form: Lyophilized powder
• Analytical methods: RP-HPLC for purity and mass spectrometry for identity, reported on the batch certificate of analysis

Research applications

• TREK-1 inhibition: In patch-clamp recordings on hTREK-1/HEK cells, PE-22-28 inhibited TREK-1 with an IC₅₀ of 0.12 nM, compared with 40 to 60 nM for spadin, and its action in vivo lasted up to 23 hours instead of 7 [1]
• Neurogenesis and synaptogenesis: PE-22-28 and its analogs induced neurogenesis in mice after 4 days of treatment, increased PSD-95 expression in cortical neurons, and were studied in the forced swimming and novelty suppressed feeding tests [1]
• Parent peptide pharmacology: Spadin bound TREK-1 with 10 nM affinity, blocked TREK-1 activity in cultured hippocampal neurons and brain slices, and increased 5-HT neuron firing in the dorsal raphe nucleus of mice [2]
• Focal ischemia models: A shortened spadin analog, mini-spadin, had a biphasic effect on TREK-1 (activation at low doses, inhibition at higher doses) and was studied in a mouse model of focal ischemia and post-stroke depression-like behavior [3]
• Analog design: Reviewed alongside retro-inverso, cyclized and shortened spadin analogs developed to increase TREK-1 inhibition and in vivo stability [4]

Reference citations

1. Djillani A. et al. (2017). Shortened spadin analogs display better TREK-1 inhibition, in vivo stability and antidepressant activity. Front Pharmacol, 8:643. PMID 28955242 · DOI
2. Mazella J. et al. (2010). Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design. PLoS Biol, 8(4):e1000355. PMID 20405001 · DOI
3. Pietri M. et al. (2019). First evidence of protective effects on stroke recovery and post-stroke depression induced by sortilin-derived peptides. Neuropharmacology, 158:107715. PMID 31325429 · DOI
4. Djillani A. et al. (2019). Fighting against depression with TREK-1 blockers: past and future. A focus on spadin. Pharmacol Ther, 194:185–198. PMID 30291907 · DOI

Compound data from PubChem CID 165437303. Literature summaries describe published preclinical research and are not claims about this product’s effects in humans or animals.