2. Academic Validation
  3. Potent, Efficacious, and Stable Cyclic Opioid Peptides with Long Lasting Antinociceptive Effect after Peripheral Administration

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

  • J Med Chem. 2020 Mar 12;63(5):2673-2687. doi: 10.1021/acs.jmedchem.9b01963.
Azzurra Stefanucci 1,  Marilisa Pia Dimmito 1,  Giorgia Macedonio 1,  Laura Ciarlo 2,  Stefano Pieretti 2,  Ettore Novellino 3,  Wei Lei 4,  Deborah Barlow 5,  Karen L Houseknecht 5,  John M Streicher 4,  Adriano Mollica 1
Affiliations

Affiliations

  • 1 Dipartimento di Farmacia, Università di Chieti-Pescara "G. d'Annunzio", Via dei Vestini 31, 66100 Chieti, Italy.
  • 2 Istituto Superiore di Sanità, Centro Nazionale Ricerca e Valutazione Preclinica e Clinica dei Farmaci, Viale Regina Elena 299, 00161 Rome, Italy.
  • 3 Dipartimento di Farmacia, Università di Napoli "Federico II", Via D. Montesano, 49, 80131 Naples, Italy.
  • 4 Department of Pharmacology, College of Medicine, University of Arizona, Tucson, Arizona 85724, United States.
  • 5 Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, Maine 04005, United States.
PMID: 31834798 DOI: 10.1021/acs.jmedchem.9b01963
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.

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