Preparation and binding properties of radioiodinated analogues of dermorphin and deltorphin with high specificity for the mu- and delta-opioid receptors.
The synthesis, purification, chemical characterization, and binding properties of two 125I-labeled analogues of dermorphin and deltorphin-I are described. Native deltorphin-I and [Lys7] dermorphin sequences were elongated by an aminopentyl chain on their C-terminal amide function and alkylated with the 125I-labeled monoiodinated derivative of Bolton-Hunter reagent (BH*). The resulting radiolabeled peptides, epsilon-BH* [Lys7] dermorphin 5-aminopentylamide and omega-BH* deltorphin-I 5-aminopentylamide, have kept most of the original properties of the parent peptides. They bind with high selectivity and specificity to the mu- (dermorphin analogue) or delta- (deltorphin-I analogue) opioid receptors from rat brain or from cells transfected with cDNAs encoding the mu and delta receptors. The autoradiographic distribution of specific binding sites for the 125I-labeled dermorphin and deltorphin-I analogues in rat brain is in complete agreement with previously reported localizations of mu- and delta-opioid receptors. The two radiolabeled peptides are the best ligands of mu- and delta-opioid receptors currently available in terms of sensitivity, specificity, and selectivity.
Gaudriault
G
G
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UPR 411-Université de Nice Sophia Antipolis, Valbonne, France.
Zsürger
N
N
Vincent
J P
JP
D000595:Amino Acid Sequence; D000701:Analgesics, Opioid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology; D007457:Iodine Radioisotopes; D008024:Ligands; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D018847:Opioid Peptides; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000302:isolation & purification; D011498:Protein Precursors / Q000138:chemical synthesis; D051381:Rats; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D012680:Sensitivity and Specificity
D000701:Analgesics, Opioid; D007457:Iodine Radioisotopes; D008024:Ligands; D009842:Oligopeptides; D018847:Opioid Peptides; D010446:Peptide Fragments; D011498:Protein Precursors; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C059567:deltorphin; C030058:dermorphin