title: Dopamine receptor modulation by Pro-Leu-Gly-NH2 analogues possessing cyclic amino acid residues at the C-terminal position.
abstract: The synthesis of several analogues of L-prolyl-L-leucylglycinamide (PLG) was carried out in which the glycinamide residue was replaced with the following cyclic amino acid residues: L- and D-prolinamide, (+)- and (-)-thiazolidine-2-carboxamide, L- and D-3,4-dehydroprolinamide, L-azetidine-2-carboxamide, L-piperidine-2-carboxamide, and L-thiazolidine-4-carboxamide to give PLG analogues 2-10, respectively. The ability of these analogues to enhance the binding of the dopamine agonist ADTN (2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene) to dopamine receptors was determined by using bovine brain tissue. All of the PLG analogues synthesized in this study enhanced the binding of ADTN to central dopamine receptors. The percent enhancement of ADTN binding produced by analogues 2,3, and 7-10 at various concentrations was comparable to the percent enhancement produced by PLG. The PLG analogues Pro-Leu-(+)-thiazolidine-2-carboxamide (4), Pro-Leu-(-)-thiazolidine-2-carboxamide (5), and Pro-Leu-L-3,4-dehydroprolinamide (6), however, produced significantly greater enhancement (2-3-fold) in ADTN binding than did PLG.
mesh_terms: D000818:Animals; D002417:Cattle; D066298:In Vitro Techniques; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D011487:Protein Conformation; D011954:Receptors, Dopamine / Q000187:drug effects*; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000378:metabolism; D014316:Tritium
chemical_list: C037078:MSH release inhibiting hormone receptor; D011954:Receptors, Dopamine; D017981:Receptors, Neurotransmitter; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D013764:Tetrahydronaphthalenes; D014316:Tritium; C011639:ADTN; D009075:MSH Release-Inhibiting Hormone