CINECA IRIS Institutional Research Information System
IRIS è la soluzione IT che facilita la raccolta e la gestione dei dati relativi alle attività e ai prodotti della ricerca. Fornisce a ricercatori, amministratori e valutatori gli strumenti per monitorare i risultati della ricerca, aumentarne la visibilità e allocare in modo efficace le risorse disponibili.
EnglishThe peptide nociceptin/orphanin FQ (N/OFQ) and the N/OFQ receptor (NOP) constitute a neuropeptidergic system that modulates various biological functions and is currently targeted for the generation of innovative drugs. In the present study dimeric NOP receptor ligands with spacers of different lengths were generated using both peptide and non-peptide pharmacophores. The novel compounds (12 peptide and 7 nonpeptide ligands) were pharmacologically investigated in a calcium mobilization assay and in the mouse vas deferens bioassay. Both structure-and conformation-Activity studies were performed. Results demonstrated that dimerization did not modify the pharmacological activity of both peptide and non-peptide pharmacophores. Moreover, when dimeric compounds were obtained with low potency peptide pharmacophores, dimerization recovered ligand potency. This effect depends on the doubling of the C-Terminal address sequence rather than the presence of an additional N-Terminal message sequence or modifications of peptide conformation.
| Autori: | |
| Autori: | Pacifico, Salvatore; Carotenuto, Alfonso; Brancaccio, Diego; Novellino, Ettore; Marzola, Erika; Ferrari, Federica; Cerlesi, Maria Camilla; Trapella, Claudio; Preti, Delia; Salvadori, Severo; Calo', Girolamo; Guerrini, Remo |
| Presenza coautori internazionali: | no |
| Data di pubblicazione: | 2017 |
| Numero degli autori: | 12 |
| Titolo: | Structure-and conformation-Activity studies of nociceptin/orphanin FQ receptor dimeric ligands |
| Supporto: | ELETTRONICO |
| Lingua: | Inglese |
| Affiliation straniere: | ITALIA |
| Sostenibilità: | NO |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1038/srep45817 |
| URL: | https://www.nature.com/articles/srep45817 |
| Codice identificativo Scopus: | 2-s2.0-85017105939 |
| Codice identificativo WOS: | WOS:000398597200001 |
| Codice identificativo Pubmed: | 28383520 |
| Rivista: | SCIENTIFIC REPORTS |
| Volume: | 7 |
| Pagina iniziale: | 45817-1 |
| Pagina finale: | 45817-14 |
| Numero di pagine: | 14 |
| Rilevanza: | Internazionale |
| Revisione (peer review): | Esperti anonimi |
| Corresponding Author: | Guerrini R |
| Note: | The study was carried out with financial support from the "FONDO DI ATENEO PER LA RICERCA SCIENTIFICA" (FAR 2015) of the University of Ferrara |
| Abstract: | The peptide nociceptin/orphanin FQ (N/OFQ) and the N/OFQ receptor (NOP) constitute a neuropeptidergic system that modulates various biological functions and is currently targeted for the generation of innovative drugs. In the present study dimeric NOP receptor ligands with spacers of different lengths were generated using both peptide and non-peptide pharmacophores. The novel compounds (12 peptide and 7 nonpeptide ligands) were pharmacologically investigated in a calcium mobilization assay and in the mouse vas deferens bioassay. Both structure-and conformation-Activity studies were performed. Results demonstrated that dimerization did not modify the pharmacological activity of both peptide and non-peptide pharmacophores. Moreover, when dimeric compounds were obtained with low potency peptide pharmacophores, dimerization recovered ligand potency. This effect depends on the doubling of the C-Terminal address sequence rather than the presence of an additional N-Terminal message sequence or modifications of peptide conformation. |
| Finanziamenti: | Nessun Finanziamento |
| Appare nelle tipologie: | 03.1 Articolo su rivista |
File in questo prodotto:
| File | Descrizione | Tipologia | Licenza | |
|---|---|---|---|---|
| srep45817.pdf | versione editoriale | Full text (versione editoriale) |  | Open Access Visualizza/Apri |
Copyright © 2021