Identification of a binding domain of the endothelin-B receptor using a selective IRL-1620-derived photoprobe

Biochemistry
Stéphane BoivinAlain Fournier

Abstract

On the basis of the structure of IRL-1620, a specific agonist of the endothelin-B receptor subtype (ET(B)), a few photosensitive analogues were developed to investigate the binding domain of the receptor. Among those, a derivative containing the photoreactive amino acid, p-benzoyl-l-phenylalanine in position 5 showed, as assessed with endothelin-A (ET(A)) and ET(B) receptor paradigms, pharmacological properties very similar to those of IRL-1620. The binding capacity of the probe was also evaluated on transfected Chinese hamster ovary (CHO) cells overexpressing the human ET(B) receptor. Data showed that binding of the radiolabeled peptide was inhibited by ET-1 and IRL-1620. Therefore, this photolabile probe was used to label the ET(B) receptor found in CHO cells. Photolabeling produced a ligand-protein complex appearing on SDS-PAGE at around 49 kDa. An excess of ET-1 or IRL-1620 completely abolished the formation of the complex, showing the selectivity of the photoprobe. Digestions of the [Bpa(5),Tyr((125)I)(6)]IRL-1620-ET(B) complex were carried out, and receptor fragments were analyzed to define the region of the receptor where the ligand interacts. Results showed that Endo Lys-C digestion gave a 3.8-kDa fragment corresponding...Continue Reading

Citations

Mar 1, 2011·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Travis P BarrGary R Strichartz
Dec 30, 2008·The Journal of Pain : Official Journal of the American Pain Society·Alla KhodorovaGary Strichartz
Mar 18, 2008·Biochimie·Jacinthe AubinAlain Fournier
May 26, 2009·Journal of Peptide Science : an Official Publication of the European Peptide Society·Jens LättigGerd Krause

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