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

ABSTRACT: d-Pen2,d-Pen5 enkephalin (DPDPE) is one of the most selective synthetic peptide agonists targeting the ?-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 ?- and ?-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.

SUBMITTER: Stefanucci A

PROVIDER: S-EPMC5392763 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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

Stefanucci Azzurra A Novellino Ettore E Mirzaie Sako S Macedonio Giorgia G Pieretti Stefano S Minosi Paola P Szűcs Edina E Erdei Anna I AI Zádor Ferenc F Benyhe Sándor S Mollica Adriano A

ACS medicinal chemistry letters 20170314 4

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 an ...[more]

PMID: 28435535

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