title: Synthesis and biological evaluation of analogues of Pro-Leu-Gly-NH2 modified at the leucyl residue.
abstract: A series of analogues of Pro-Leu-Gly-NH2 (PLG) in which the leucine residue has been replaced with the aliphatic amino acids L-isoleucine, L-2-aminohexanoic acid (Ahx), L-2-aminopentanoic acid, and L-2-aminobutanoic acid and the aromatic amino acids L-phenylalanine, L-phenylglycine, L- and D-2-amino-4-phenylbutanoic acid, L-O-methyltyrosine, and L-4-nitrophenylalanine have been synthesized. These analogues were tested for their ability to enhance the binding of the dopamine receptor agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN) to striatal dopamine receptors. Two of the above analogues, Pro-Ahx-Gly-NH2 (3) and Pro-Phe-Gly-NH2 (6), showed significant activity in this assay system. Pro-Ahx-Gly-NH2 produced a 16% enhancement of ADTN binding at 0.1 microM, while Pro-Phe-Gly-NH2 enhanced the binding of ADTN by 31% at a concentration of 1 microM.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis 55455.
authors.forename: R L
authors.initials: RL
authors.lastname: Johnson
authors.forename: R J
authors.initials: RJ
authors.lastname: Bontems
authors.forename: K E
authors.initials: KE
authors.lastname: Yang
authors.forename: R K
authors.initials: RK
authors.lastname: Mishra
mesh_terms: D000818:Animals; D002417:Cattle; D007930:Leucine; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017448:Receptors, Dopamine D2; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000378:metabolism
chemical_list: D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D013764:Tetrahydronaphthalenes; C020196:2-amino-5,6-dihydroxytetralin; C055207:prolyl-leucyl-glycine; D009075:MSH Release-Inhibiting Hormone; D007930:Leucine