Scopus
🔓 Açık Erişim
Discovery of novel µ-opioid receptor inverse agonist from a combinatorial library of tetrapeptides through structure-based virtual screening
Molecules · Ekim 2019
Makale Bilgileri
DergiMolecules
Yayın TarihiEkim 2019
Cilt / Sayfa24
Scopus ID2-s2.0-85074160603
Erişim🔓 Açık Erişim
Özet
Morphine, oxycodone, fentanyl, and other µ-opioid receptors (MOR) agonists have been used for decades in antinociceptive therapies. However, these drugs are associated with numerous side effects, such as euphoria, addiction, respiratory depression, and adverse gastrointestinal reactions, thus, circumventing these drawbacks is of extensive importance. With the aim of identifying novel peptide ligands endowed with MOR inhibitory activity, we developed a virtual screening protocol, including receptor-based pharmacophore screening, docking studies, and molecular dynamics simulations, which was used to filter an in-house built virtual library of tetrapeptide ligands. The three top-scored compounds were synthesized and subjected to biological evaluation, revealing the identity of a hit compound (peptide 1) endowed with appreciable MOR inverse agonist effect and selectivity over δ-opioid receptors. These results confirmed the reliability of our computational approach and provided a promising starting point for the development of new potent MOR modulators.
Yazarlar (7)
1
Giulio Poli
2
Marilisa Pia Dimmito
3
Adriano Mollica
4
Gokhan Zengin
ORCID: 0000-0001-6548-7823
5
Sandor Benyhe
6
Ferenc Zádor
7
Azzurra Stefanucci
Anahtar Kelimeler
Docking
Peptides
Pharmacophore
Virtual screening
µ-opioid receptor
Kurumlar
Magyar Tudomanyos Akademia
Budapest Hungary
Selçuk Üniversitesi
Selçuklu Turkey
Università di Pisa
Pisa Italy
University of G. d'Annunzio Chieti and Pescara
Chieti Italy
Metrikler
20
Atıf
7
Yazar
5
Anahtar Kelime