Journal article

Site-directed mutagenesis of the rat beta(1)-adrenoceptor. Involvement of Tyr(356(7.43)) in ( /-)cyanopindolol but not ( /-)[(125)Iodo]cyanopindolol binding

LA Rezmann-Vitti, SNS Louis, TL Nero, GP Jackman, CA Machida, WJ Louis

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER | Published : 2004

Abstract

To determine the role played by Tyr(356 (7.43)) in the rat beta(1)-adrenoceptor in binding the antagonists (+/-)cyanopindolol (4-[3-(t-butylamino]-3-(2'-cyano-indoloxy)-2-propanolol) and its iodinated analogue (+/-)[(125)Iodo]cyanopindolol (1-(t-butylamino]-3-(2'-cyano-3'-iodo-indoloxy)-2-propanolol), Tyr(356 (7.43)) was mutated to either Phe or Ala and binding affinities determined for wild type and mutant rat beta(1)-adrenoceptors. Our results indicate that Tyr(356 (7.43)) is important for (+/-)cyanopindolol, but not (+/-)[(125)Iodo]cyanopindolol, binding and that (+/-)cyanopindolol adopts a "reverse" binding orientation whereas (+/-)[(125)Iodo]cyanopindolol cannot be accommodated in this ..

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