Opioid ligands with extraordinarily high μ-selectivity: Dermorphin tetrapeptides containing thymine-modified alanine residues

• Published in: FEBS letters 1994-09, Vol.351 (3), p.308-310
• Main Authors: Kharkevich, D.A., Sumbatyan, N.V., Topin, A.N., Chichenkov, O.N., Zaitsev, S.V., Korshunova, G.A.
• Format: Article
• Language: English
• Subjects: 3-(Thyminyl-1)alanine; Ad, 1-adamantyl; Alanine - metabolism; Amino Acid Sequence; Analgesics, Opioid - chemistry; Analgesics, Opioid - metabolism; Analgesics, Opioid - pharmacology; Animals; Brain - drug effects; Brain - metabolism; DAGO, H-Tyr-d-Ala-Gly-MePhe-Gly-ol; Dermorphin analogue; DM/1-4/, dermorphin tetrapeptide, H-Tyr-d-Ala-Phe-Gly-NH2; DSLET, H-Tyr-d-Ser-Gly-Phe-Leu-Thr-OH; GPI, guinea-pig ileum; Guinea Pigs; Ileum - drug effects; Ileum - metabolism; In Vitro Techniques; Male; Mice; Molecular Sequence Data; MVD, mouse vas deferens; Oligopeptides - chemistry; Oligopeptides - metabolism; Oligopeptides - pharmacology; Opioid; Opioid Peptides; Rats; Receptors, Opioid, mu - drug effects; Receptors, Opioid, mu - metabolism; Rodentia; Tal, 3-(thyminyl-1)alanine; Thymine - metabolism; Vas Deferens - drug effects; Vas Deferens - metabolism; μ-selective ligand
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(94)00849-3

Four new [ d-MetO 2]dermorphin tetrapeptides with substituted N- and C-terminal groups and a thymine-modified alanine residue at position 4 were prepared and tested for their activity. All analogues were found to be μ-opioid receptor ligands. Two of them, H-Tyr- d-MetO-Phe-TalNHR (R=H, Ad) displayed an extremely highu μ-opioid receptor selectivity comparable with that of the most μ-selective agonists among opioid peptides.