Opioid Receptor Activity and Analgesic Potency of DPDPE Peptide Analogues Containing a Xylene Bridge

Azzurra Stefanucci, Ettore Novellino, Sako Mirzaie, Giorgia Macedonio, Stefano Pieretti, Paola Minosi, Edina Szűcs, A. Erdei, Ferenc Zádor, S. Benyhe, Adriano Mollica

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

d-Pen2,d-Pen5 enkephalin (DPDPE) is one of the most selective synthetic peptide agonists targeting the δ-opioid receptor. Three cyclic analogues of DPDPE containing a xylene bridge in place of disulfide bond have been synthesized and fully characterized as opioid receptors agonists. The in vitro activity was investigated showing a good affinity of 7a-c for μ- and δ-receptors. In vivo biological assays revealed that 7b is the most potent analogue with the ability to maintain high level of analgesia from 15 to 60 min following intracerebroventricular (i.c.v.) administration, whereas DPDPE was slightly active until 45 min. Compound 7b induced long lasting analgesia also after subcutaneous administration, whereas DPDPE was inactive.

Original languageEnglish
Pages (from-to)449-454
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume8
Issue number4
DOIs
Publication statusPublished - Apr 13 2017

Keywords

  • antinociception
  • DPDPE
  • Opioids
  • peptides
  • xylene bridge

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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    Stefanucci, A., Novellino, E., Mirzaie, S., Macedonio, G., Pieretti, S., Minosi, P., Szűcs, E., Erdei, A., Zádor, F., Benyhe, S., & Mollica, A. (2017). Opioid Receptor Activity and Analgesic Potency of DPDPE Peptide Analogues Containing a Xylene Bridge. ACS Medicinal Chemistry Letters, 8(4), 449-454. https://doi.org/10.1021/acsmedchemlett.7b00044