Compound monograph
Spadin
Spadin is a sortilin-propeptide-derived peptide reported to interact with sortilin and to inhibit the TREK-1 potassium channel, and the parent design from which PE 22-28 was derived.
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Identity & nomenclature
Spadin is a sortilin-propeptide-derived peptide reported to interact with sortilin and to inhibit the TREK-1 potassium channel, and the parent design from which PE 22-28 was derived.
Spadin derives from the propeptide released during sortilin maturation. Sortilin is also called neurotensin receptor 3. This entry specifies the eighteen-residue Tyr-extended form; the unqualified name spadin and the label PE(12-28) do not resolve the seventeen-versus-eighteen-residue distinction. The founding study describes a Tyr0 radioiodination site. Its labeled binding probe is a separate reagent, and an assay described only as spadin does not establish that every experiment used the same terminal form. PE 22-28 is a seven-residue designed truncation of the same propeptide sequence.
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Molecular properties
| Molecular formula | C96H142N26O22 |
|---|---|
| Molecular mass | 2012.3 Da |
| CAS Registry Number | 1270083-24-3 |
| PubChem CID | 91826106 |
| One-letter sequence | YAPLPRWSGPIGVSWGLR |
Eighteen residues with free termini. This record specifies the Tyr-extended form YAPLPRWSGPIGVSWGLR. The seventeen-residue sortilin-propeptide segment PE(12-28) is APLPRWSGPIGVSWGLR; the added tyrosine changes the residue composition by 163.06 Da.
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Structural characteristics
The founding study reported reciprocal immunoprecipitation of sortilin and TREK-1 and colocalization in cortical neurons. Binding assays reported approximately 10 nM affinity, and electrophysiology measured inhibition of TREK-1 activity in transfected cells, cultured hippocampal neurons and brain slices. A later study designed PE 22-28 from blood degradation products and measured TREK-1 inhibition in hTREK-1/HEK cells at approximately 0.1 nM, against 40-60 nM for the spadin comparator. That source is internally inconsistent about which peptide carries which value: its abstract and results report 0.12 nM for PE 22-28 and 0.10 nM for the Gly22-Ala analog, while its figure legend and discussion transpose the two. No single figure is reproduced here as though the source agreed with itself. These results establish the experimental design relationship; they do not establish endogenous production of the seven-residue peptide. The Tyr extension and radioiodination state must be tracked when comparing reagents.
Terminal features: Free N-terminus, Free C-terminal carboxyl.
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Molecular targets & mechanisms
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Analytical considerations
The first question for any sample is whether it begins Tyr-Ala or Ala: the tyrosine residue adds 163.06 Da monoisotopic, 163.18 Da average, and N-terminal fragmentation localises it. State which convention a reported figure uses; the recorded mass on this entry is an average mass. Radioiodinated Tyr-containing binding probes used in this literature are separate reagents and are not chemically identical to unlabelled spadin. For PE 22-28, verify the exact seven residues and the free acid, and exclude the Gly22-Ala analog and the biotinylated derivatives used in the same experiments — a shared TREK-1 response does not distinguish them.
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Verified bibliography
- Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design.current
Mazella J, Pétrault O, Lucas G, Deval E, Béraud-Dufour S, Gandin C, El-Yacoubi M, Widmann C, Guyon A, Chevet E, Taouji S, Conductier G, Corinus A, Coppola T, Gobbi G, Nahon JL, Heurteaux C, Borsotto M
PLoS biology · 2010-04-13 · Journal Article
- Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity.current
Djillani A, Pietri M, Moreno S, Heurteaux C, Mazella J, Borsotto M
Frontiers in pharmacology · 2017-09-12 · Journal Article
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Methodology & citation verification
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