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Neuropeptides Involved in Pain Control

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (15 October 2019) | Viewed by 5976

Special Issue Editors


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Guest Editor
Department of Pharmacy, "G. d'Annunzio" University, Via dei Vestini 31, 66100 Chieti, Italy
Interests: opioid peptides; cannabinoids; amino acids; nutraceuticals; bioactive compounds
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Pharmacy, "G. d’Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy
Interests: food; chemicals; sustainability; synthesis; peptides
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neuropeptides are well-defined chemical molecules, produced and released by the central nervous system and peripheral. They are involved in the transmission, modulation, and perception of physiological, neuropathic, and inflammatory pain. The development of novel nonpeptide agonists/antagonists, molecular cloning techniques, and transgenic animal models helps to define their functions in the nociceptive cascade, revealing a complex pattern of molecular mechanisms. Often, they are co-localized with neurotransmitters at the same nerve ending, blocking or enhancing their effects. For example, the calcitonin-gene-related peptide (CGRP) and neuropeptide tyrosine (NPY) are expressed and released from non-neuronal cells, acting via the same receptors as their neuronal counterparts. Peptides are endowed with a pleiotropic function, which is responsible for their plasticity under normal and experimental conditions, and redundancy, which may account for the poor performance of individual neuropeptide inhibitors in clinical trials. Accordingly, this Special Issue is focused on the design, synthesis, and biological evaluation of novel neuropeptides with the hope to replace or, at least, complement the use of opiate drugs, leading to increased efficacy and reduced adverse effects.

Prof. Adriano Mollica
Dr. Azzurra Stefanucci
Guest Editors

Manuscript Submission Information

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Keywords

  • Neuropeptides
  • Pain
  • Opioid system
  • Cannabinoids
  • Peptide synthesis
  • Peptidomimetics
  • Peptide application
  • Peptide cell-targeting
  • Peptide design

Published Papers (1 paper)

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Research

16 pages, 2453 KiB  
Article
Discovery of Novel µ-Opioid Receptor Inverse Agonist from a Combinatorial Library of Tetrapeptides through Structure-Based Virtual Screening
by Giulio Poli, Marilisa Pia Dimmito, Adriano Mollica, Gokhan Zengin, Sandor Benyhe, Ferenc Zador and Azzurra Stefanucci
Molecules 2019, 24(21), 3872; https://doi.org/10.3390/molecules24213872 - 27 Oct 2019
Cited by 16 | Viewed by 4760
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Neuropeptides Involved in Pain Control)
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