Abstract
In search of new selective antagonists and/or agonists for the human melanocortin receptor subtypes hMC1R to hMC5R to elucidate the specific biological roles of each GPCR, we modified the structures of the superagonist MT-II (Ac-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]-NH(2)) and the hMC3R/hMC4R antagonist SHU9119 (Ac-Nle-c[Asp-His-D-Nal(2')-Arg-Trp-Lys]-NH(2)) by replacing the His-d-Phe and His-d-Nal(2') fragments in MT-II and SHU9119, respectively, with Aba-Xxx (4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one-Xxx) dipeptidomimetics (Xxx=D-Phe/pCl-D-Phe/D-Nal(2')). Employment of the Aba mimetic yielded novel selective high affinity hMC3R and hMC3R/hMC5R antagonists.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Benzazepines / chemical synthesis
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Benzazepines / chemistry*
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Benzazepines / pharmacology
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Chemistry, Pharmaceutical / methods*
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Drug Design
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Humans
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Inhibitory Concentration 50
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Ligands
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Magnetic Resonance Spectroscopy
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Models, Chemical
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Molecular Conformation
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Peptides / chemistry
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Receptor, Melanocortin, Type 3 / antagonists & inhibitors*
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Receptor, Melanocortin, Type 3 / chemistry*
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Receptors, Corticotropin / antagonists & inhibitors
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Receptors, Corticotropin / chemistry
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Receptors, Melanocortin
Substances
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4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one
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Benzazepines
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Ligands
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Peptides
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Receptor, Melanocortin, Type 3
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Receptors, Corticotropin
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Receptors, Melanocortin
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melanocortin 5 receptor