Development of a Photolabile Ligand for the EndothelinA Receptor of Endothelin

Actions of endothelin ET are usually mediated through the socalled endothelinA or B ETAor ETBreceptors. As part of our ongoing research program, we are studying the characterization of the ETAreceptor using specific photolabile ligands. Starting with the ETAspecific antagonist TTA386 as a leading compound we developed new ETAspecific antagonists containing the photolabile amino acid, pbenzoylphenylalanine Bpa. Following a Bpa peptide scan, with either the L or Disomer, we found that Dphenylalanine6 of TTA386 can be substituted with either L or DBpa and gives analogs showing antagonistic properties, in an ETAreceptor preparation rat aorta, very similar to those of TTA386 itself. No agonistic or antagonistic properties were measured with these derivatives in an ETBpharmacological preparation guinea pig lung parenchyma. Thus, these new ligands appear as very promising probes for the characterization of the ETAreceptor.