title: Novel selective human melanocortin-3 receptor ligands: use of the 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one (Aba) scaffold.
abstract: In search of new selective antagonists and/or agonists for the human melanocortin receptor subtypes hMC1R to hMC5R to elucidate the specific biological roles of each GPCR, we modified the structures of the superagonist MT-II (Ac-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]-NH(2)) and the hMC3R/hMC4R antagonist SHU9119 (Ac-Nle-c[Asp-His-D-Nal(2')-Arg-Trp-Lys]-NH(2)) by replacing the His-d-Phe and His-d-Nal(2') fragments in MT-II and SHU9119, respectively, with Aba-Xxx (4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one-Xxx) dipeptidomimetics (Xxx=D-Phe/pCl-D-Phe/D-Nal(2')). Employment of the Aba mimetic yielded novel selective high affinity hMC3R and hMC3R/hMC5R antagonists.
authors.affiliation: Department of Organic Chemistry, Vrije Universiteit Brussel, B-1050 Brussels, Belgium. sballet@vub.ac.be
authors.forename: Steven
authors.initials: S
authors.lastname: Ballet
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Mayorov
authors.forename: Minying
authors.initials: M
authors.lastname: Cai
authors.forename: Dagmara
authors.initials: D
authors.lastname: Tymecka
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Chandler
authors.forename: Erin S
authors.initials: ES
authors.lastname: Palmer
authors.forename: Karolien Van
authors.initials: KV
authors.lastname: Rompaey
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Misicka
authors.forename: Dirk
authors.initials: D
authors.lastname: Tourwé
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Hruby
mesh_terms: D001552:Benzazepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry; D044104:Receptor, Melanocortin, Type 3 / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D018043:Receptors, Corticotropin / Q000037:antagonists & inhibitors / Q000737:chemistry; D044101:Receptors, Melanocortin
chemical_list: C520912:4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one; D001552:Benzazepines; D008024:Ligands; D010455:Peptides; D044104:Receptor, Melanocortin, Type 3; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; C086971:melanocortin 5 receptor