کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2008795 | 1066444 | 2005 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Isolation and characterization of antagonist and agonist peptides to the human melanocortin 1 receptor
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
We identified a large number of peptide mimotopes of the adrenocorticotropic hormone (ACTH) and the α-melanocyte stimulating hormone (α-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 108 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 μM, two strong agonists, EC50 = 25 and 14 nM and a partial antagonist, IC50 = 36 μM. This work confirmed the modulator agonist role of the regions 11-12 of α-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 α-MSH having a partial antagonist effect. These results may be useful in the development of potential agonists or antagonists of the hMC1R.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Peptides - Volume 26, Issue 11, November 2005, Pages 2302-2313
Journal: Peptides - Volume 26, Issue 11, November 2005, Pages 2302-2313
نویسندگان
Stéphane Bonetto, Isabelle Carlavan, Daniel Baty,