Opioid pseudopeptides containing heteroaromatic or heteroaliphatic nuclei.
In lieu of H-Dmt-Tic-OH, H-Dmt-analogues included 2-amino-3(1H-benzoimidazol-2-yl)-propionic acid, N(Bzl)Gly, L-octahydroindole-2-carboxylic acid, [3S-(3alpha,4abeta, 8abeta)]-decahydro-3-isoquinoline carboxylic acid, benzimidazole-, pyridoindole- or spiroinden-derivatives, or C-terminally modified. L- or D-Ala, Sar, or Pro were spacers between aromatic nuclei. Only H-Dmt-(Xaa-)-pyridoindole exhibited high affinities with delta and mu antagonism. The peptides competed equally against [3H]DPDPE (delta agonist) or [3H]N,N(CH3)2-Dmt-Tic-OH (delta antagonist) signaling a single delta binding site. The data confirm the importance of Tic for delta affinity and antagonism, while heterocyclic or heteroaliphatic nuclei, or spacer exert effects on mu- and delta-receptor properties.
Balboni
G
G
Department of Toxicology, University of Cagliari, I-09126, Cagliari, Italy.
Salvadori
S
S
Guerrini
R
R
Bianchi
C
C
Santagada
V
V
Calliendo
G
G
Bryant
S D
SD
Lazarus
L H
LH
D000409:Alanine / Q000737:chemistry; D001562:Benzimidazoles / Q000737:chemistry; D001665:Binding Sites; D002243:Carbolines / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry; D004151:Dipeptides / Q000737:chemistry; D007546:Isoquinolines / Q000737:chemistry; D007700:Kinetics; D008024:Ligands; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011392:Proline / Q000737:chemistry; D011422:Propionates / Q000737:chemistry; D011487:Protein Conformation; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D044005:Tetrahydroisoquinolines; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry
D001562:Benzimidazoles; D002243:Carbolines; D002264:Carboxylic Acids; D004151:Dipeptides; D007546:Isoquinolines; D008024:Ligands; D010455:Peptides; D011422:Propionates; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D044005:Tetrahydroisoquinolines; C100957:tyrosyl-1,2,3,4-tetrahydro-3--isoquinoline-carbonyl-alanine; C076121:2',6'-dimethyltyrosine; D014443:Tyrosine; D012694:Serine; D011392:Proline; C031000:benzimidazole; C029658:propionic acid; D000409:Alanine