Repozytorium
Wyszukaj
Kolekcje
Inne
Synthesis, Biological Activity and Molecular Docking of Chimeric Peptides Targeting Opioid and NOP Receptors
Autorzy
Rok wydania
2022
Czasopismo
International Journal of Molecular Sciences
Numer woluminu
23
Strony
12700/1-12700/18
DOI
10.3390/ijms232012700
Kolekcja
Język
Angielski
Typ publikacji
Artykuł
Recently, mixed opioid/NOP agonists came to the spotlight for their favorable functional profiles and promising outcomes in clinical trials as novel analgesics. This study reports on two novel chimeric peptides incorporating the fragment Tyr-c[D-Lys-Phe-Phe]Asp-NH2 (RP-170), a cyclic peptide with high affinity for µ and κ opioid receptors (or MOP and KOP, respectively), conjugated with the peptide Ac-RYYRIK-NH2, a known ligand of the nociceptin/orphanin FQ receptor (NOP), yielding RP-170-RYYRIK-NH2 (KW-495) and RP-170-Gly3-RYYRIK-NH2 (KW-496). In vitro, the chimeric KW-496 gained affinity for KOP, hence becoming a dual KOP/MOP agonist, while KW-495 behaved as a mixed MOP/NOP agonist with low nM affinity. Hence, KW-495 was selected for further in vivo experiments. Intrathecal administration of this peptide in mice elicited antinociceptive effects in the hot-plate test; this action was sensitive to both the universal opioid receptor antagonist naloxone and the selective NOP antagonist SB-612111. The rotarod test revealed that KW-495 administration did not alter the mice motor coordination performance. Computational studies have been conducted on the two chimeras to investigate the structural determinants at the basis of the experimental activities, including any role of the Gly3 spacer.
Słowa kluczowe
opioid receptors, nociceptin receptor, chimeric peptides, calcium mobilization assay, antitociceptive test, docking studies
Licencja otwartego dostępu
Licencja na prawach której można swobodnie kopiować, rozprowadzać, zmieniać i remiksować objęty prawem autorskim utwór (Utwór-przedmiot prawa autorskiego) pod warunkiem podania imienia i nazwiska autora utworu pierwotnego oraz źródła pochodzenia utworu.
Pełny tekst licencji: https://creativecommons.org/licenses/by/3.0/pl/legalcode
Adres publiczny
http://dx.doi.org/10.3390/ijms232012700
Strona internetowa wydawcy
Podobne publikacje
Pharmacological characterization of endomorphin-2-based cyclic pentapeptides with methylated phenylalanine residues.
Perlikowska Renata, Malfacini Davide, Cerlesi Maria Camilla, Calò Girolamo, Piekielna Justyna, Floriot Léonore, Henry Tiphaine, do-Rego Jean Claude, Tömböly Csaba, Kluczyk Alicja, Janecka Anna
Synthesis of mixed MOR/KOR efficacy cyclic opioid peptide analogs with antinociceptive activity after systemic administration.
Perlikowska Renata, Piekielna Justyna, Gentilucci Luca, De Marco Rossella, Cerlesi Maria Camilla, Calò Girolamo, Artali Roberto, Tömböly Csaba, Kluczyk Alicja, Janecka Anna
Synthesis of mixed opioid affinity cyclic endomorphin-2 analogues with fluorinated phenylalanines.
Piekielna Justyna, Perlikowska Renata, do-Rego Jean Claude, do-Rego Jean-Luc, Cerlesi Maria Camilla, Calò Girolamo, Kluczyk Alicja, Łapiński Krzysztof, Tömböly Csaba, Janecka Anna