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Volume 8 Medicinal Chemistry
ISSN: 2161-0444 Medicinal Chemistry 2018
June 14-15, 2018
June 14-15, 2018 | Barcelona, Spain
10th World Congress on
Medicinal Chemistry and Drug Design
In vitro and in vivo activity of opioid cyclopeptide with mu/delta agonist profile
Katarzyna Gach-Janczak1, Justyna Piekielna-Ciesielska1, Anna Adamska-Bartłomiejczyk1, Karol Wtorek1, Federica Ferrari2, Girolamo Calo 2, Agata
Szymaszkiewicz1 and Anna Janecka1
1Medical University of Lodz, Poland
1University of Ferrara, Italy
C entrally acting opioid agonists, such as morphine, are the most widely used analgesics for the treatment of severe pain.
Among the three types of classic opioid receptors, mu, delta and kappa, the mu receptor was identified as primarily
responsible for the pain-relieving effects but also responsible for a number of undesired side effects, including sedation,
respiratory depression, inhibition of gastrointestinal transit, tolerance and physical dependence. In the previous decades,
chemists and pharmacologists focused on obtaining analogs with high selectivity for one opioid receptor type. More recently,
the development of compounds with mixed opioid profile is gaining a lot of interest eg. synergistic antinociceptive effects in
response to the mu and delta receptor activation were observed in several in vivo studies. In this study we have shown that the
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 profile. This new analog
showed improved antinociception in the hot-plate test as compared to the parent peptide 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. To the best of our knowledge, it is the first reported β-arrestin biased opioid analog of a peptide
structure. Our data are in accordance with earlier reports indicating that various in vivo activities of opioid agonists arise not
only from the activation of one or more opioid receptors, but also from promoting G-protein or β-arrestin pathways.
Biography
Katarzyna Gach-Janczak has been working in the Department of Biomolecular Chemistry at Medical University of Lodz since 2006, first as a PhD student, then as an
Assistant and now as an Assistant Professor. In May 2010, she defended her Doctoral thesis. She completed her Post-doctoral training in the Laboratory of Neuronal and
Neuroendocrine Differentiation and Communication, University of Rouen (France). Her area of scientific interests is bidirectional. She is searching for new analgesics
based on the structure of the endogenous opioid peptides and studying synthetic heterocyclic compounds as potential anticancer agents. She has published 43 research
papers in international journals.
Katarzyna Gach-Janczak et al., Med chem (Los Angeles) 2018, Volume 8
DOI: 10.4172/2161-0444-C1-039