Identification of a human estrogen receptor α tetrapeptidic fragment with dual antiproliferative and anti-nociceptive action.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
24 01 2023
24 01 2023
Historique:
received:
31
03
2022
accepted:
12
01
2023
entrez:
24
1
2023
pubmed:
25
1
2023
medline:
27
1
2023
Statut:
epublish
Résumé
The synthetic peptide ERα17p (sequence: PLMIKRSKKNSLALSLT), which corresponds to the 295-311 region of the human estrogen receptor α (ERα), induces apoptosis in breast cancer cells. In mice and at low doses, it promotes not only the decrease of the size of xenografted triple-negative human breast tumors, but also anti-inflammatory and anti-nociceptive effects. Recently, we have shown that these effects were due to its interaction with the seven-transmembrane G protein-coupled estrogen receptor GPER. Following modeling studies, the C-terminus of this peptide (sequence: NSLALSLT) remains compacted at the entrance of the GPER ligand-binding pocket, whereas its N-terminus (sequence: PLMI) engulfs in the depth of the same pocket. Thus, we have hypothesized that the PLMI motif could support the pharmacological actions of ERα17p. Here, we show that the PLMI peptide is, indeed, responsible for the GPER-dependent antiproliferative and anti-nociceptive effects of ERα17p. By using different biophysical approaches, we demonstrate that the NSLALSLT part of ERα17p is responsible for aggregation. Overall, the tetrapeptide PLMI, which supports the action of the parent peptide ERα17p, should be considered as a hit for the synthesis of new GPER modulators with dual antiproliferative and anti-nociceptive actions. This study highlights also the interest to modulate GPER for the control of pain.
Identifiants
pubmed: 36693877
doi: 10.1038/s41598-023-28062-9
pii: 10.1038/s41598-023-28062-9
pmc: PMC9873809
doi:
Substances chimiques
Estrogen Receptor alpha
0
Estrogens
0
Peptides
0
Receptors, G-Protein-Coupled
0
GPER1 protein, human
0
estrogen receptor alpha (295-311), human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1326Informations de copyright
© 2023. The Author(s).
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