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

被引：27

作者：

Giolitti, A

Cucchi, P

Renzetti, AR

Rotondaro, L

Zappitelli, S

Maggi, CA

机构：

[1] Menarini Ric, Dept Drug Design, Florence, Italy

[2] Menarini Ric, Dept Pharmacol, Florence, Italy

[3] Menarini Ric, Dept Biotechnol, Rome, Italy

来源：

NEUROPHARMACOLOGY | 2000年 / 39卷 / 08期

关键词：

tachykinins; NK2-receptor; MEN; 11420; SR; 48968; mutagenesis;

D O I：

10.1016/S0028-3908(00)00008-3

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

A series of 14 mutants on nine selected residues of the human tachykinin NK2 receptor was produced and stably transfected into CHO cells to investigate the binding of the peptide MEN 11420 and the nonpeptide SR 48968 antagonists. The main interactions found for MEN 11420 were with Thr171, Tyr206, Tyr266 and Phe270. In the case of SR 48968 crucial residues were Tyr266 and Tyr289. While some overlapping of the binding sites exists, the binding modes suggested by this study appear not to allow structural correlation, and therefore general SAR, between these two antagonists. (C) 2000 Elsevier Science Ltd. All rights reserved.

引用

页码：1422 / 1429

页数：8

共 27 条

[1]

[Anonymous], NUCL ACIDS RES

[2]

BHOGAL N, 1994, J BIOL CHEM, V269, P27269

[3] MEN 11420 (Nepadutant), a novel glycosylated bicyclic peptide tachykinin NK2 receptor antagonist [J].