The melanocortin receptor system

A target for multiple degenerative diseases

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The melanocortin receptor system consists of five closely related G-protein coupled receptors (MC1R, MC2R, MC3R, MC4R and MC5R). These receptors are involved in many of the key biological functions for multicellular animals, including human beings. The natural agonist ligands for these receptors are derived by processing of a primordial animal gene product, proopiomelanocortin (POMC). The ligand for the MC2R is ACTH (Adrenal Corticotropic Hormone), a larger processed peptide from POMC. The natural ligands for the other 4 melanocortin receptors are smaller peptides including α-melanocyte stimulating hormone (α-MSH) and related peptides from POMC (β-MSH and γ-MSH). They all contain the sequence His-Phe-Arg-Trp that is conserved throughout evolution. Thus, there has been considerable difficulty in developing highly selective ligands for the MC1R, MC3R, MC4R and MC5R. In this brief review, we discuss the various approaches that have been taken to design agonist and antagonist analogues and derivatives of the POMC peptides that are selective for the MC1R, MC3R, MC4R and MC5R receptors, via peptide, nonpeptide and peptidomimetic derivatives and analogues and their differential interactions with receptors that may help account for these selectivities.

Original languageEnglish (US)
Pages (from-to)488-496
Number of pages9
JournalCurrent Protein and Peptide Science
Volume17
Issue number5
StatePublished - Aug 1 2016

Fingerprint

Melanocortin Receptors
Pro-Opiomelanocortin
Melanocyte-Stimulating Hormones
Ligands
Peptides
Receptor, Melanocortin, Type 4
Peptidomimetics
Animals
Peptide Receptors
Derivatives
G-Protein-Coupled Receptors
Hormones
Genes
Processing

Keywords

  • ACTH: adrenal corticotropic hormone
  • AGRP: agouti related protein
  • ASIP: agouti signaling protein
  • GPCRs: G-protein coupled receptors
  • Melanocortin Receptors (MCRs: MC1R, MC2R, MC3R, MC4R, MC5R)
  • MT-II: Ac-Nle-c[Asp, D-Phe, Lys]α-MSH(4-10)-NH, (Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH)
  • MTI: Ac-Ser-Tyr-Ser-Met-Glu-His-DPhe-Arg-Trp-Gly-Lys-Pro-Val- NH
  • POMC: Proopiomelanocortin
  • SHU9119: Ac- Nle-c[Asp, D-Nal(2’), Lys]α-MSH(4-10)-NH, (Ac-Nle-c[Asp-His- D-Nal(2’)-Arg-Trp-Lys]-NH)
  • Α-MSH: α -melanocyte stimulate hormone

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

The melanocortin receptor system : A target for multiple degenerative diseases. / Cai, Minying; Hruby, Victor J.

In: Current Protein and Peptide Science, Vol. 17, No. 5, 01.08.2016, p. 488-496.

Research output: Contribution to journalArticle

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abstract = "The melanocortin receptor system consists of five closely related G-protein coupled receptors (MC1R, MC2R, MC3R, MC4R and MC5R). These receptors are involved in many of the key biological functions for multicellular animals, including human beings. The natural agonist ligands for these receptors are derived by processing of a primordial animal gene product, proopiomelanocortin (POMC). The ligand for the MC2R is ACTH (Adrenal Corticotropic Hormone), a larger processed peptide from POMC. The natural ligands for the other 4 melanocortin receptors are smaller peptides including α-melanocyte stimulating hormone (α-MSH) and related peptides from POMC (β-MSH and γ-MSH). They all contain the sequence His-Phe-Arg-Trp that is conserved throughout evolution. Thus, there has been considerable difficulty in developing highly selective ligands for the MC1R, MC3R, MC4R and MC5R. In this brief review, we discuss the various approaches that have been taken to design agonist and antagonist analogues and derivatives of the POMC peptides that are selective for the MC1R, MC3R, MC4R and MC5R receptors, via peptide, nonpeptide and peptidomimetic derivatives and analogues and their differential interactions with receptors that may help account for these selectivities.",
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AU - Hruby, Victor J

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AB - The melanocortin receptor system consists of five closely related G-protein coupled receptors (MC1R, MC2R, MC3R, MC4R and MC5R). These receptors are involved in many of the key biological functions for multicellular animals, including human beings. The natural agonist ligands for these receptors are derived by processing of a primordial animal gene product, proopiomelanocortin (POMC). The ligand for the MC2R is ACTH (Adrenal Corticotropic Hormone), a larger processed peptide from POMC. The natural ligands for the other 4 melanocortin receptors are smaller peptides including α-melanocyte stimulating hormone (α-MSH) and related peptides from POMC (β-MSH and γ-MSH). They all contain the sequence His-Phe-Arg-Trp that is conserved throughout evolution. Thus, there has been considerable difficulty in developing highly selective ligands for the MC1R, MC3R, MC4R and MC5R. In this brief review, we discuss the various approaches that have been taken to design agonist and antagonist analogues and derivatives of the POMC peptides that are selective for the MC1R, MC3R, MC4R and MC5R receptors, via peptide, nonpeptide and peptidomimetic derivatives and analogues and their differential interactions with receptors that may help account for these selectivities.

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