AI Article Synopsis
- A series of cyclic pentapeptides were created and tested for their effects on human melanocortin receptors, focusing on the impact of alkyl chain length in omega-amino acids.
- Compound 2 emerged as a potent agonist for the hMC-4R receptor, demonstrating significantly higher potency compared to alpha-MSH with an EC50 value of 15.4 nM.
- Additionally, Compound 2 exhibited a strong selectivity for hMC-4R over hMC-1R, highlighting the importance of lactam ring size and structure in developing selective agonists.
Article Abstract
A series of cyclic pentapeptides, c(His-D-Phe-Arg-Trp-Z) (Z=omega-amino acid), were prepared and biologically evaluated. The effects of increasing alkyl chain length of omega-amino acid on the functional activities and the receptor binding affinities for human melanocortin receptors (hMC-Rs) were studied. Compound 2 was an agonist for hMC-4R with an EC50 value of 15.4 nM, which was 4.7 times more potent than that of alpha-MSH. Compound 2 also showed a 4.3-fold higher hMC-4R selectivity over hMC-1R, thus providing us with information concerning size and chemical structure of the lactam ring for the development of the agonist with hMC-4R selectivity.
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| http://dx.doi.org/10.1016/j.bmcl.2006.04.050 | DOI Listing |
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Design of cyclic peptides with agonist activity at melanocortin receptor-4.
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Research Center, Pharmaceutical R&D Division, Asahi Kasei Pharma Corporation, Izunokuni 410-2321, Japan.
Article Synopsis
- A series of cyclic pentapeptides were created and tested for their effects on human melanocortin receptors, focusing on the impact of alkyl chain length in omega-amino acids.
- Compound 2 emerged as a potent agonist for the hMC-4R receptor, demonstrating significantly higher potency compared to alpha-MSH with an EC50 value of 15.4 nM.
- Additionally, Compound 2 exhibited a strong selectivity for hMC-4R over hMC-1R, highlighting the importance of lactam ring size and structure in developing selective agonists.
1H-NMR studies on a potent and selective antagonist at human melanocortin receptor 4 (hMC-4R).
Biopolymers
April 2003
Department of Drug Metabolism, Merck Research Laboratories, Rahway, NJ, USA.
Melanocortin receptor 4 (MC-4R) is involved in the regulation of energy balance and body weight, and recognizes alpha-, beta-, and gamma-melanocyte stimulating hormones (alpha-, beta-, gamma-MSH). In the search for compounds that regulate food intake and body weight, two synthetic lactam-derivative ligands of alpha-MSH were discovered, MTII and SHU9119. MTII is an agonist and reduces food intake in rats, whereas SHU9119 is an antagonist, and increases food intake and body weight in rats.
View Article and Find Full Text PDFSelective, high affinity peptide antagonists of alpha-melanotropin action at human melanocortin receptor 4: their synthesis and biological evaluation in vitro.
J Med Chem
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Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
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View Article and Find Full Text PDFPotent and selective peptide agonists of alpha-melanotropin action at human melanocortin receptor 4: their synthesis and biological evaluation in vitro.
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Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
alpha-Melanotropin (alphaMSH) and several of its derivatives are potent but not selective agonists at melanocortin receptors 3, 4, and 5 present in the brain (MC3-5R). To differentiate between the physiological role of hMC-4R (believed to be involved in regulation of energy balance) from those of melanocortin receptors 3 and 5, potent and receptor-specific agonists are needed. Therefore, the cyclic derivatives of alphaMSH of a general structure, cyclo(X-His-d-Phe-Arg-Trp-Y)-NH(2), where X is succinic acid or an omega-amino-carboxylic acid, and Y is an alpha,omega-di-amino-carboxylic acid or an omega-carboxy-alpha-amino acid, were prepared and tested in binding assays and in cAMP assays on CHO cells expressing hMC3-5R.
View Article and Find Full Text PDFAnalogs of MTII, lactam derivatives of alpha-melanotropin, modified at the N-terminus, and their selectivity at human melanocortin receptors 3, 4, and 5.
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Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, New Jersey, 07065, USA.
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