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• W1964980903 abstract "We identified a large number of peptide mimotopes of the adrenocorticotropic hormone (ACTH) and the alpha-melanocyte stimulating hormone (alpha-MSH) to analyze better the structure-function relationships of these hormones with the human MC1 receptor (hMC1R). We have investigated the use of phage-display technology to isolate specific peptides of this receptor by using three monoclonal anti-ACTH antibodies (mAbs). A library of 10(8) phage-peptides displaying randomized decapeptides was constructed and used to select phage-peptides that bind to mAbs. Forty-five phage-peptides have been isolated and from their amino acid sequences, we have identified two consensus sequences, EXFRWGKPA and WGXPVGKP, corresponding to the regions 5-13 and 9-16 of ACTH, respectively. A biological assay on cells expressing the hMC1-R was developed to determine the capacity of phage-peptides to stimulate the receptor. Only two phage-peptides showed detectable activity. Thirty-one peptides were synthesized to analyze their biological effect. We identified two weak agonists, EC50=16 and 11 microM, two strong agonists, EC50=25 and 14 nM and a partial antagonist, IC50=36 microM. This work confirmed the modulator agonist role of the regions 11-12 of alpha-MSH and ACTH, and the importance of the methionine residue at position 4 for the stimulation of the hMC1-R. We also identified analogues of the regions 8-17 of ACTH that exhibited a weak activator effect, and of one analogue of the N-terminal regions 1-9 of ACTH and alpha-MSH having a partial antagonist effect. These results may be useful in the development of potential agonists or antagonists of the hMC1R." @default.
• W1964980903 created "2016-06-24" @default.
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• W1964980903 creator A5025296603 @default.
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• W1964980903 date "2005-11-01" @default.
• W1964980903 modified "2023-09-25" @default.
• W1964980903 title "Isolation and characterization of antagonist and agonist peptides to the human melanocortin 1 receptor" @default.
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• W1964980903 doi "https://doi.org/10.1016/j.peptides.2005.04.002" @default.
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