Special Issue "The Melanocortin System: From Ligands to Receptors and Accessory Systems"

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (15 March 2023) | Viewed by 3293

Special Issue Editors

Department of Chemistry & Biochemistry, College of Science and College of Medicine, University of Arizona, Tucson, AZ 85721, USA
Interests: melanocyte stimulating hormones (MSHs); melanocortin receptors (MCRs); melanocortin structure function relationships; melanocortin biological activities; melanocortin pharmacological activities; melanocortin physiological activities; melanocortin structures; melanocortin tissue distribution; melanocortin roles in health and disease
Department of Chemistry & Biochemistry, College of Science; Arizona Cancer Center, College of Medicine, University of Arizona, Tucson, AZ 85721, USA
Interests: melanocortin; drug design and discovery; GPCR; peptide and peptidomimetics; pigmentation; melanoma; high throughput screening
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Special Issue Information

Dear Colleagues,

The melanocortin system is a critical, complex biological system of peptide hormones produced from the precursor protein proopiomelanocortin (POMC), 5 G-protein coupled receptors MC1R, MC2R, MC3R, MC4R and MC5R, plus complex downstream signaling pathways that modulate and control many important biological processes in all animal species, including humans. These include pigmentation, feeding behavior, sexual function, temperature control, and many others that are still being discovered as well as many diseases associated with these functions. Original manuscripts and reviews dealing with all aspects of this system including ligand design, biological activities, and mechanisms from a chemical, biological, physical, pharmacological, physiological, or medical perspective are welcome.

Prof. Dr. Victor J. Hruby
Prof. Dr. Minying Cai
Guest Editors

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Keywords

  • melanocortin system
  • melanotropins
  • drug design

Published Papers (3 papers)

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Research

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Article
Structure/Function Studies on the Activation Motif of Two Non-Mammalian Mrap1 Orthologs, and Observations on the Phylogeny of Mrap1, Including a Novel Characterization of an Mrap1 from the Chondrostean Fish, Polyodon spathula
Biomolecules 2022, 12(11), 1681; https://doi.org/10.3390/biom12111681 - 12 Nov 2022
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Abstract
In derived bony vertebrates, activation of the melanocortin-2 receptor (Mc2r) by its ACTH ligand requires chaperoning by the Mc2r accessory protein (Mrap1). The N-terminal domain of the non-mammalian tetrapod MRAP1 from chicken (c; Gallus gallus) has the putative activation motif, W18 [...] Read more.
In derived bony vertebrates, activation of the melanocortin-2 receptor (Mc2r) by its ACTH ligand requires chaperoning by the Mc2r accessory protein (Mrap1). The N-terminal domain of the non-mammalian tetrapod MRAP1 from chicken (c; Gallus gallus) has the putative activation motif, W18D19Y20I21, and the N-terminal domain in the neopterygian ray-finned fish Mrap1 from bowfin (bf; Amia calva) has the putative activation motif, Y18D19Y20I21. The current study used an alanine-substitution paradigm to test the hypothesis that only the Y20 position in the Mrap1 ortholog of these non-mammalian vertebrates is required for activation of the respective Mc2r ortholog. Instead, we found that for cMRAP1, single alanine-substitution resulted in a gradient of inhibition of activation (Y20 >> D19 = W18 > I21). For bfMrap1, single alanine-substitution also resulted in a gradient of inhibition of activation (Y20 >> D19 > I21 > Y18). This study also included an analysis of Mc2r activation in an older lineage of ray-finned fish, the paddlefish (p), Polyodon spathula (subclass Chondronstei). Currently no mrap1 gene has been found in the paddlefish genome. When pmc2r was expressed alone in our CHO cell/cAMP reporter gene assay, no activation was observed following stimulation with ACTH. However, when pmc2r was co-expressed with either cmrap1 or bfmrap1 robust dose response curves were generated. These results indicate that the formation of an Mc2r/Mrap1 heterodimer emerged early in the radiation of the bony vertebrates. Full article
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Review

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Review
Melanogenesis and the Targeted Therapy of Melanoma
Biomolecules 2022, 12(12), 1874; https://doi.org/10.3390/biom12121874 - 14 Dec 2022
Cited by 1 | Viewed by 1044
Abstract
Pigment production is a unique character of melanocytes. Numerous factors are linked with melanin production, including genetics, ultraviolet radiation (UVR) and inflammation. Understanding the mechanism of melanogenesis is crucial to identify new preventive and therapeutic strategies in the treatment of melanoma. Here, we [...] Read more.
Pigment production is a unique character of melanocytes. Numerous factors are linked with melanin production, including genetics, ultraviolet radiation (UVR) and inflammation. Understanding the mechanism of melanogenesis is crucial to identify new preventive and therapeutic strategies in the treatment of melanoma. Here, we reviewed the current available literatures on the mechanisms of melanogenesis, including the signaling pathways of UVR-induced pigment production, MC1R’s central determinant roles and MITF as a master transcriptional regulator in melanogenesis. Moreover, we further highlighted the role of targeting BRAF, NRAS and MC1R in melanoma prevention and treatment. The combination therapeutics of immunotherapy and targeted kinase inhibitors are becoming the newest therapeutic option in advanced melanoma. Full article
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Review
Ligands for Melanocortin Receptors: Beyond Melanocyte-Stimulating Hormones and Adrenocorticotropin
Biomolecules 2022, 12(10), 1407; https://doi.org/10.3390/biom12101407 - 01 Oct 2022
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Abstract
The discovery of melanocortins in 1916 has resulted in more than 100 years of research focused on these peptides. Extensive studies have elucidated well-established functions of melanocortins mediated by cell surface receptors, including MSHR (melanocyte-stimulating hormone receptor) and ACTHR (adrenocorticotropin receptor). Subsequently, three [...] Read more.
The discovery of melanocortins in 1916 has resulted in more than 100 years of research focused on these peptides. Extensive studies have elucidated well-established functions of melanocortins mediated by cell surface receptors, including MSHR (melanocyte-stimulating hormone receptor) and ACTHR (adrenocorticotropin receptor). Subsequently, three additional melanocortin receptors (MCRs) were identified. Among these five MCRs, MC3R and MC4R are expressed primarily in the central nervous system, and are therefore referred to as the neural MCRs. Since the central melanocortin system plays important roles in regulating energy homeostasis, targeting neural MCRs is emerging as a therapeutic approach for treating metabolic conditions such as obesity and cachexia. Early efforts modifying endogenous ligands resulted in the development of many potent and selective ligands. This review focuses on the ligands for neural MCRs, including classical ligands (MSH and agouti-related peptide), nonclassical ligands (lipocalin 2, β-defensin, small molecules, and pharmacoperones), and clinically approved ligands (ACTH, setmelanotide, bremelanotide, and several repurposed drugs). Full article
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