Structure–activity relationship of cyclic peptide penta-c[Asp-His6-DPhe7-Arg8-Trp9-Lys]-NH2 at the human melanocortin-1 and -4 receptors: His6 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.