Potent, Efficacious, and Stable Cyclic Opioid Peptides with Long Lasting Antinociceptive Effect after Peripheral Administration

Azzurra Stefanucci, Marilisa Pia Dimmito, Giorgia Macedonio, Laura Ciarlo, Stefano Pieretti, Ettore Novellino, Wei Lei, Deborah Barlow, Karen L Houseknecht, John M Streicher, Adriano Mollica

Research output: Contribution to journalArticlepeer-review

Abstract

Four novel fluorinated cyclic analogues of biphalin with excellent to modest binding affinity for μ-, δ-, and κ-receptors were synthesized. The cyclic peptides have a combination of piperazine or hydrazine linker with or without a xylene bridge. Among the ligands, MACE3 demonstrated a better activity than biphalin after intravenous administration, and its corresponding analogue incorporating the hydrazine linker (MACE2) was able to induce longer lasting analgesia following subcutaneous administration. An analogue of MACE2 containing 2,6-dimethyl-l-tyrosine (MACE4) showed the best potency and in vivo antinociceptive activity of this series.

Original languageEnglish
Pages (from-to)2673-2687
Number of pages15
JournalJournal of Medicinal Chemistry
Volume63
Issue number5
DOIs
Publication statusPublished - Mar 12 2020

Fingerprint Dive into the research topics of 'Potent, Efficacious, and Stable Cyclic Opioid Peptides with Long Lasting Antinociceptive Effect after Peripheral Administration'. Together they form a unique fingerprint.

Cite this