Modified melanocortin tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 at the arginine side chain with ureas and thioureas

C. G. Joseph, N. B. Sorensen, M. S. Wood, Z. Xiang, M. C. Moore, Carrie Haskell-Luevano

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The Ac-His-DPhe-Arg-Trp-NH2 tetrapeptide is a nonselective melanocortin agonist and replacement of Arg in the tetrapeptide with acidic, basic or neutral amino acids results in reduced potency at the melanocortin receptor (MCR) isoforms (MC1R and MC3-5R). To determine the importance of the positive charge and the guanidine moiety for melanocortin activity, a series of urea- and thiourea-substituted tetrapeptides were designed. Replacement of Arg with Lys or ornithine reduced agonist activity at the mouse mMC1 and mMC3-5 receptors, thus supporting the hypothesis that the guanidine moiety is important for receptor potency, particularly at the MC3-5 receptors. The Arg side chain-modified tetrapeptides examined in this study include substituted phenyl, naphthyl, and aliphatic urea and thiourea residues using a Lys side-chain template. These ligands elicit full-agonist pharmacology at the mouse MCRs examined in this study.

Original languageEnglish (US)
Pages (from-to)297-307
Number of pages11
JournalJournal of Peptide Research
Volume66
Issue number5
DOIs
StatePublished - Nov 2005

Keywords

  • MC3R
  • MC4R
  • Melanocortin
  • Melanotropin
  • Obesity
  • Tetrapeptide
  • Thiourea
  • Urea
  • α-melanocyte-stimulating hormone

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