Giolitti A, Cucchi P, Renzetti A R, Rotondaro L, Zappitelli S, Maggi C A
Department of Drug Design, Menarini Ricerche, Via Sette Santi 3, Firenze, Italy.
Neuropharmacology. 2000 Jun 8;39(8):1422-9. doi: 10.1016/s0028-3908(00)00008-3.
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 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.
在人速激肽NK(2)受体的九个选定残基上产生了一系列14个突变体，并将其稳定转染到CHO细胞中，以研究肽类MEN 11420和非肽类SR 48968拮抗剂的结合情况。发现MEN 11420的主要相互作用位点是苏氨酸171、酪氨酸206、酪氨酸266和苯丙氨酸270。对于SR 48968而言，关键残基是酪氨酸266和酪氨酸289。虽然存在一些结合位点的重叠，但本研究提出的结合模式似乎不允许这两种拮抗剂之间存在结构相关性，因此也不存在一般的构效关系。
