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

Bioorg Med Chem Lett. 2003 Apr 7;13(7):1307-11. doi: 10.1016/s0960-894x(03)00114-8.

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.

MeSH terms

  • Amino Acid Substitution
  • Cell Survival / drug effects
  • Histidine / chemistry*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / pharmacology
  • Receptor, Melanocortin, Type 4
  • Receptors, Corticotropin / agonists*
  • Receptors, Melanocortin
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Peptides, Cyclic
  • Receptor, Melanocortin, Type 4
  • Receptors, Corticotropin
  • Receptors, Melanocortin
  • Histidine