The Gly 4 and/or Tyr 5 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 Gly 4-Xaa 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.
Opioid peptides. Synthesis and biological properties of dermorphin related hexapeptides
BALBONI, GIANFRANCO;
1990-01-01
Abstract
The Gly 4 and/or Tyr 5 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 Gly 4-Xaa 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.
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