title: Structure-activity relationship of cyclic peptide penta-c[Asp-His(6)-DPhe(7)-Arg(8)-Trp(9)-Lys]-NH(2) at the human melanocortin-1 and -4 receptors: His(6) substitution.
abstract: A series of MT-II related cyclic peptides, based on potent but non-selective hMC4R agonist (Penta-c[Asp-His(6)-DPhe(7)-Arg(8)-Trp(9)-Lys]-NH(2)) was prepared in which His(6) residue was systematically substituted. Two of the most interesting peptides identified in this study are Penta-c[Asp-5-ClAtc-DPhe-Arg-Trp-Lys]-NH(2) and Penta-c[Asp-5-ClAtc-DPhe-Cit-Trp-Lys]-NH(2) which are potent hMC4R agonists and are either inactive or weak partial agonists (not tested for their antagonist activities) in hMC1R, hMC3R and hMC5R agonist assays.
authors.affiliation: Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA. adrian.cheung@roche.com
authors.forename: Adrian Wai-Hing
authors.initials: AW
authors.lastname: Cheung
authors.forename: Waleed
authors.initials: W
authors.lastname: Danho
authors.forename: Joseph
authors.initials: J
authors.lastname: Swistok
authors.forename: Lida
authors.initials: L
authors.lastname: Qi
authors.forename: Grazyna
authors.initials: G
authors.lastname: Kurylko
authors.forename: Karen
authors.initials: K
authors.lastname: Rowan
authors.forename: Mitch
authors.initials: M
authors.lastname: Yeon
authors.forename: Lucia
authors.initials: L
authors.lastname: Franco
authors.forename: Xin-Jie
authors.initials: XJ
authors.lastname: Chu
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Keith
authors.initials: K
authors.lastname: Yagaloff
mesh_terms: D019943:Amino Acid Substitution; D002470:Cell Survival / Q000187:drug effects; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000494:pharmacology; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000819:agonists*; D044101:Receptors, Melanocortin; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D010456:Peptides, Cyclic; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D006639:Histidine