Structure-activity relationship of linear peptide Bu-His-DPhe-Arg-Trp-Gly-NH(2) at the human melanocortin-1 and -4 receptors: arginine substitution.
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.
Cheung
Adrian Wai-Hing
AW
Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA. adrian.cheung@roche.com
Danho
Waleed
W
Swistok
Joseph
J
Qi
Lida
L
Kurylko
Grazyna
G
Franco
Lucia
L
Yagaloff
Keith
K
Chen
Li
L
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
D006146:Guanidines; D009842:Oligopeptides; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D001120:Arginine; C004711:dicyandiamido