Synthesis and pharmacology of α/β3-peptides based on the melanocortin agonist Ac-His-d Phe-Arg-Trp-NH2 sequence

Anamika Singh, Srinivasa R. Tala, Viktor Flores, Katie Freeman, Carrie Haskell-Luevano

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The melanocortin-3 and -4 receptors are expressed in the brain and play key roles in regulating feeding behavior, metabolism, and energy homeostasis. In the present study, incorporation of β3-amino acids into a melanocortin tetrapeptide template was investigated. Four linear α/β3-hybrid tetrapeptides were designed with the modifications at the Phe, Arg, and Trp residues in the agonist sequence Ac-His-dPhe-Arg-Trp-NH2. The most potent mouse melanocortin-4 receptor (mMC4R) agonist, Ac-His-dPhe-Arg-β3hTrp-NH2 (8) showed 35-fold selectivity versus the mMC3R. The study presented here has identified a new template with heterogeneous backbone for designing potent and selective melanocortin receptor ligands.

Original languageEnglish (US)
Pages (from-to)568-572
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume6
Issue number5
DOIs
StatePublished - May 14 2015

Keywords

  • peptidomimetics
  • α/β-peptides
  • β-amino acids

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