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.
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.
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
Rowan
Karen
K
Yeon
Mitch
M
Franco
Lucia
L
Chu
Xin-Jie
XJ
Chen
Li
L
Yagaloff
Keith
K
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
D010456:Peptides, Cyclic; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D006639:Histidine