Molecular determinants of peptide and nonpeptide NK-2 receptor antagonistsbinding sites of the human tachykinin NK-2 receptor by site-directed mutagenesis

A series of 14 mutants on nine selected residues of the human tachykinin NK 2 receptor was produced and stably transfected into CHO cells to investigat e the binding of the peptide MEN 11420 and the nonpeptide SR 48968 antagoni sts. The main interactions found for MEN 11420 were with Thr171, Tyr206, Ty r266 and Phe270. In the case of SR 48968 crucial residues were Tyr266 and T yr289. While some overlapping of the binding sites exists, the binding mode s suggested by this study appear not to allow structural correlation, and t herefore general SAR, between these two antagonists. (C) 2000 Elsevier Scie nce Ltd. All rights reserved.