title: New opioid affinity labels containing maleoyl moiety.
abstract: Opioid receptor binding properties and pharmacological profiles of novel peptides containing maleoyl function were determined in order to develop new affinity labels. Based on the enkephalin structure peptide ligands were synthesized and tested. Both in in vitro receptor binding experiments and pharmacological studies, all ligands showed agonist character with relatively high affinity (Ki values in the nanomolar range) and good to moderate selectivity. Replacement of Gly2 in the enkephalin frame with D-Ala led to higher affinities with a small decrease in selectivity. The longer peptide chains resulted in compounds with high percentage (up to 86%) of irreversible binding. The selectivity pattern of the ligands is in good agreement with the data obtained from the pharmacological assays (guinea pig ileum and mouse vas deferens bioassays). The newly synthesized peptides could be used in further studies in order to determine more detailed characteristics of the ligand-receptor interaction.
authors.affiliation: Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Szeged.
authors.forename: I
authors.initials: I
authors.lastname: Szatmári
authors.forename: G
authors.initials: G
authors.lastname: Orosz
authors.forename: A Z
authors.initials: AZ
authors.lastname: Rónai
authors.forename: E
authors.initials: E
authors.lastname: Makó
authors.forename: K
authors.initials: K
authors.lastname: Medzihradszky
authors.forename: A
authors.initials: A
authors.lastname: Borsodi
mesh_terms: D000345:Affinity Labels; D019943:Amino Acid Substitution; D000818:Animals; D001921:Brain / Q000378:metabolism; D004745:Enkephalins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D008298:Maleates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008566:Membranes / Q000378:metabolism; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D018847:Opioid Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000345:Affinity Labels; D004745:Enkephalins; D008024:Ligands; D008298:Maleates; D018847:Opioid Peptides; D011957:Receptors, Opioid