In vitro and in vivo activity of opioid cyclopeptide with mu/delta agonist profile biased toward β-arrestin

Publication date: Available online 22 April 2018
Source:Peptides
Author(s): Katarzyna Gach-Janczak, Justyna Piekielna-Ciesielska, Anna Adamska-Bartłomiejczyk, Karol Wtorek, Federica Ferrari, Girolamo Calo, Agata Szymaszkiewicz, Joanna Piasecka-Zelga, Anna Janecka
Replacement of the tyrosine residue in the mu-selective opioid ligand Tyr-c[D-Lys-Phe-Asp]NH2 with 2',6'-dimethyltyrosine (Dmt) produced a cyclopeptide Dmt-c[D-Lys-Phe-Asp]NH2 with mu/delta opioid receptor agonist profile. This new analog showed improved antinociception in the hot-plate test as compared to the parent but also significantly inhibited the gastrointestinal transit. Using the bioluminescence resonance energy transfer (BRET) assay it was shown that this analog was biased toward β-arrestin.

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