Opioid ligands with extraordinarily high mu-selectivity: dermorphin tetrapeptides containing thymine-modified alanine residues.
Four new [D-MetO2]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 mu-opioid receptor ligands. Two of them, H-Tyr-D-MetO-Phe-TalNHR (R = H, Ad) displayed an extremely high mu-opioid receptor selectivity comparable with that of the most mu-selective agonists among opioid peptides.
Kharkevich
D A
DA
Department of Pharmacology, I.M. Sechenov Moscow Medical Academy, Russian Federation.
Sumbatyan
N V
NV
Topin
A N
AN
Chichenkov
O N
ON
Zaitsev
S V
SV
Korshunova
G A
GA
D000409:Alanine / Q000378:metabolism*; D000595:Amino Acid Sequence; D000701:Analgesics, Opioid / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D018847:Opioid Peptides; D051381:Rats; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism*; D013941:Thymine / Q000378:metabolism*; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism
D000701:Analgesics, Opioid; D009842:Oligopeptides; D018847:Opioid Peptides; D017450:Receptors, Opioid, mu; C030058:dermorphin; D000409:Alanine; D013941:Thymine