TY - JOUR
T1 - Potent, Efficacious, and Stable Cyclic Opioid Peptides with Long Lasting Antinociceptive Effect after Peripheral Administration
AU - Stefanucci, Azzurra
AU - Dimmito, Marilisa Pia
AU - Macedonio, Giorgia
AU - Ciarlo, Laura
AU - Pieretti, Stefano
AU - Novellino, Ettore
AU - Lei, Wei
AU - Barlow, Deborah
AU - Houseknecht, Karen L.
AU - Streicher, John M.
AU - Mollica, Adriano
N1 - Publisher Copyright:
Copyright © 2019 American Chemical Society.
PY - 2020/3/12
Y1 - 2020/3/12
N2 - 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.
AB - 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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U2 - 10.1021/acs.jmedchem.9b01963
DO - 10.1021/acs.jmedchem.9b01963
M3 - Article
C2 - 31834798
AN - SCOPUS:85077704775
SN - 0022-2623
VL - 63
SP - 2673
EP - 2687
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 5
ER -