title: Dopamine receptor modulation by a highly rigid spiro bicyclic peptidomimetic of Pro-Leu-Gly-NH2.
abstract: A peptidomimetic analogue of Pro-Leu-Gly-NH2 (PLG), compound 3, has been synthesized that contains a highly constrained spiro bicyclic type-II beta-turn mimic. Peptidomimetic 3 enhanced the binding of the dopamine receptor agonist ADTN to dopamine receptors by 40% at 10(-6) M. At this same concentration PLG enhanced the binding of ADTN by 26%. Like PLG, 3 exhibited a bell-shaped dose-response curve with the maximum effect occurring at a concentration of 10(-6) M. Because of the highly rigid nature of the spiro bicyclic type-II beta-turn constraint found in 3, these results lend strong support for the hypothesis that the biologically active conformation of PLG is a type-II beta-turn.
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, Minneapolis 55455.
authors.forename: M J
authors.initials: MJ
authors.lastname: Genin
authors.forename: R K
authors.initials: RK
authors.lastname: Mishra
authors.forename: R L
authors.initials: RL
authors.lastname: Johnson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D002417:Cattle; D015259:Dopamine Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D011487:Protein Conformation; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000378:metabolism; D014316:Tritium
chemical_list: D001643:Bridged Bicyclo Compounds; D015259:Dopamine Agents; D009842:Oligopeptides; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D014316:Tritium; C011639:ADTN; C029463:prolyl-lysyl-glycinamide