Abstract
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.
MeSH terms
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Alanine / chemistry
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Benzimidazoles / chemistry
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Binding Sites
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Carbolines / chemistry
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Carboxylic Acids / chemistry
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Dipeptides / chemistry
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Isoquinolines / chemistry
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Kinetics
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Ligands
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Peptides / chemical synthesis
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Peptides / chemistry*
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Proline / chemistry
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Propionates / chemistry
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Protein Conformation
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Receptors, Opioid, delta / agonists
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Receptors, Opioid, delta / antagonists & inhibitors
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Receptors, Opioid, delta / chemistry
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Receptors, Opioid, delta / metabolism
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Receptors, Opioid, mu / agonists
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Receptors, Opioid, mu / antagonists & inhibitors
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Receptors, Opioid, mu / chemistry*
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Receptors, Opioid, mu / metabolism
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Serine / chemistry
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Tetrahydroisoquinolines*
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Tyrosine / analogs & derivatives*
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Tyrosine / chemistry
Substances
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Benzimidazoles
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Carbolines
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Carboxylic Acids
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Dipeptides
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Isoquinolines
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Ligands
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Peptides
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Propionates
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Receptors, Opioid, delta
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Receptors, Opioid, mu
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Tetrahydroisoquinolines
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tyrosyl-1,2,3,4-tetrahydro-3--isoquinoline-carbonyl-alanine
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2',6'-dimethyltyrosine
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Tyrosine
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Serine
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Proline
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benzimidazole
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propionic acid
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Alanine