Structure-activity relationship of linear peptide Bu-His-DPhe-Arg-Trp-Gly-NH(2) at the human melanocortin-1 and -4 receptors: arginine substitution

Bioorg Med Chem Lett. 2002 Sep 2;12(17):2407-10. doi: 10.1016/s0960-894x(02)00459-6.

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.

MeSH terms

  • Amino Acid Substitution
  • Arginine
  • Binding Sites
  • Guanidines
  • Humans
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / pharmacology
  • Protein Binding
  • Receptor, Melanocortin, Type 4
  • Receptors, Corticotropin / agonists*
  • Receptors, Melanocortin
  • Structure-Activity Relationship

Substances

  • Guanidines
  • Oligopeptides
  • Receptor, Melanocortin, Type 4
  • Receptors, Corticotropin
  • Receptors, Melanocortin
  • Arginine
  • dicyandiamido