The Gly4 and/or Tyr5 residues in dermorphin hexapeptide (H-Tyr-d-Ala-Phe-Gly-Tyr-Pro-OH) were replaced by Nα-methyl- or d-amino acids in order to examine the effect on opioid activity. Two pseudopeptides (H-Tyr-d-Ala-Phe-Gly-ψ (NHCO)-Xaa-Pro-OH, Xaa - Tyr or Phe) in which the Gly4Xaa bond is reversed, were also prepared. Metabolic stability, analgesia and selectivity of these compounds for different receptor populations have been investigated. Results suggest that the 12 new analogues showed a negligible affinity for the K binding site and some selectivity for μ- or δ receptors. In some cases the analgesic potencies seems to be related to enzymatic stability of the peptides. © 1990.
Opioid peptides. Synthesis and biological properties of dermorphin, related hexapeptides
SALVADORI, Severo;MARASTONI, Mauro;BOREA, Pier Andrea;TOMATIS, Roberto
1990
Abstract
The Gly4 and/or Tyr5 residues in dermorphin hexapeptide (H-Tyr-d-Ala-Phe-Gly-Tyr-Pro-OH) were replaced by Nα-methyl- or d-amino acids in order to examine the effect on opioid activity. Two pseudopeptides (H-Tyr-d-Ala-Phe-Gly-ψ (NHCO)-Xaa-Pro-OH, Xaa - Tyr or Phe) in which the Gly4Xaa bond is reversed, were also prepared. Metabolic stability, analgesia and selectivity of these compounds for different receptor populations have been investigated. Results suggest that the 12 new analogues showed a negligible affinity for the K binding site and some selectivity for μ- or δ receptors. In some cases the analgesic potencies seems to be related to enzymatic stability of the peptides. © 1990.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
