title: Synthesis and dopamine receptor modulating activity of 3-substituted gamma-lactam peptidomimetics of L-prolyl-L-leucyl-glycinamide.
abstract: gamma-Lactam peptidomimetic 2 of Pro-Leu-Gly-NH(2) (PLG) was substituted at the 3-position with isobutyl, butyl, and benzyl moieties to give the PLG peptidomimetics 3-5, respectively. These compounds were synthesized to test the hypothesis that attaching a hydrophobic moiety to the lactam ring to mimic the isobutyl side chain of the leucyl residue of PLG would increase the dopamine receptor modulating activity of such peptidomimetics. These peptidomimetics were tested for their ability to enhance the binding of [(3)H]-N-propylnorapomorphine to dopamine receptors isolated from bovine striatal membranes. The rank order of effectiveness of the 3-substituent was benzyl > n-butyl > isobutyl > H.
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Kristine
authors.initials: K
authors.lastname: Dolbeare
authors.forename: Giuseppe F
authors.initials: GF
authors.lastname: Pontoriero
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Gupta
authors.forename: Ram K
authors.initials: RK
authors.lastname: Mishra
authors.forename: Rodney L
authors.initials: RL
authors.lastname: Johnson
mesh_terms: D000818:Animals; D002417:Cattle; D003342:Corpus Striatum / Q000378:metabolism; D015259:Dopamine Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009075:MSH Release-Inhibiting Hormone / Q000737:chemistry*; D008968:Molecular Conformation; D018716:Molecular Mimicry; D011869:Radioligand Assay; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D015259:Dopamine Agents; D007769:Lactams; D011954:Receptors, Dopamine; D009075:MSH Release-Inhibiting Hormone