title: Structure-activity relationship of linear peptide Bu-His-DPhe-Arg-Trp-Gly-NH(2) at the human melanocortin-1 and -4 receptors: histidine substitution.
abstract: Systematic substitution of His(6) residue using non-selective hMC4R pentapeptide agonist (Bu-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2)) as the template led to the identification of Bu-Atc(6)(2-aminotetraline-2-carboxylic acid)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2) which showed moderate selectivity towards hMC4R over hMC1R. Further SAR studies resulted in the discovery of Penta-5-BrAtc(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2) and Penta-5-Me(2)NAtc(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2) which are potent hMC4R agonists and are inactive 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: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000242:Cyclic AMP / Q000096:biosynthesis; D006639:Histidine; D006801:Humans; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000819:agonists* / Q000378:metabolism; D044101:Receptors, Melanocortin; D013329:Structure-Activity Relationship
chemical_list: C474662:Bu-His(6)-Phe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2); D009842:Oligopeptides; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D006639:Histidine; D000242:Cyclic AMP