A new series of 12 dermorphin tetrapeptides, W-Tyr-D-MetO-Phe-Xaa-Y (W = H, H2NC—(NH); Xaa = Gly, Sar, D-Ala; Y = OH, OCH3, NH2) were prepared by traditional methods in solution and tested for opioid activity. In binding studies based on displacement of μ, δ, and k opioid receptor selective radiolabels from guinea pig brain membranes, the new analogues showed a negligible affinity for the k bindingsite and a preference for μ overδ preceptors with an evident dependence on N- and/or C-terminal modifications; H-Tyr-D-MetO-Phe-GIy-OCH3was shown to be one of the most selective ktreceptor ligands reported to date. All these tetrapeptides display dose-related naloxone-reversible antinociceptive effects following intracerebroventricular (icv) or subcutaneous (sc) administrations in mice, In comparison to morphine, H-Tyr-D-MetO-Phe-Sar-NH2 and the guanidino derivative H2NC=(NH)-Tyr-D-MetO-Phe-Gly-NH2showed lower affinity for μ,δ, and k sites but exceptionally stronger analgesia: respectively th...
Synthesis and activity profiles of new dermorphin-(1-4) peptide analogues
MARASTONI, Mauro;SALVADORI, Severo;BOREA, Pier Andrea;TOMATIS, Roberto
1987
Abstract
A new series of 12 dermorphin tetrapeptides, W-Tyr-D-MetO-Phe-Xaa-Y (W = H, H2NC—(NH); Xaa = Gly, Sar, D-Ala; Y = OH, OCH3, NH2) were prepared by traditional methods in solution and tested for opioid activity. In binding studies based on displacement of μ, δ, and k opioid receptor selective radiolabels from guinea pig brain membranes, the new analogues showed a negligible affinity for the k bindingsite and a preference for μ overδ preceptors with an evident dependence on N- and/or C-terminal modifications; H-Tyr-D-MetO-Phe-GIy-OCH3was shown to be one of the most selective ktreceptor ligands reported to date. All these tetrapeptides display dose-related naloxone-reversible antinociceptive effects following intracerebroventricular (icv) or subcutaneous (sc) administrations in mice, In comparison to morphine, H-Tyr-D-MetO-Phe-Sar-NH2 and the guanidino derivative H2NC=(NH)-Tyr-D-MetO-Phe-Gly-NH2showed lower affinity for μ,δ, and k sites but exceptionally stronger analgesia: respectively th...I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
