title: Structure-activity relationship of linear peptide Bu-His-DPhe-Arg-Trp-Gly-NH(2) at the human melanocortin-1 and -4 receptors: arginine substitution.
abstract: A series of pentapeptides, based on Bu-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2) and modified at the Arg(8) position, was prepared and pharmacologically characterized. Peptides containing either cyanoguanidine or acylguanidine, two substantially less basic arginine surrogates, were found to retain the agonist activity of the parent peptide at both hMC1R and hMC4R. This study unequivocally shows that the positive charge of Arg(8) is not essential for efficient interactions of our pentapeptide with both hMC1R and hMC4R.
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: Lucia
authors.initials: L
authors.lastname: Franco
authors.forename: Keith
authors.initials: K
authors.lastname: Yagaloff
authors.forename: Li
authors.initials: L
authors.lastname: Chen
mesh_terms: D019943:Amino Acid Substitution; D001120:Arginine; D001665:Binding Sites; D006146:Guanidines; D006801:Humans; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D011485:Protein Binding; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000819:agonists*; D044101:Receptors, Melanocortin; D013329:Structure-Activity Relationship
chemical_list: D006146:Guanidines; D009842:Oligopeptides; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D001120:Arginine; C004711:dicyandiamido