Protein structure based rational design of ecdysone agonists |
| |
Authors: | Graham Holmwood Michael Schindler |
| |
Affiliation: | Bayer CropScience AG, Alfred-Nobel-Str. 50, 40789 Monheim, Germany;Universität Wuppertal, Fachbereich Mathematik und Naturwissenschaften, Gaußstraße 20, Wuppertal, 42119, Germany |
| |
Abstract: | We review the impact of protein X-ray crystallography on the rational design of insecticides that act as agonists of the ligand-binding domain of the Ecdysone receptor (EcR). As the EcR is a target specific to insects, these compounds potentially constitute new chemical classes of safe insecticides. The increased insight relative to that from ligand-only based (Quantitative) Structure–Activity Relations (QSARs), classical 2D-Hansch type or 3D-CoMFA/CoMSIA (Comparative Molecular Field/Similarity Analysis), is discussed. The importance of protein X-ray structure determination in support of the discovery process is stressed as the simplistic lock-and-key picture fails due to the remarkable flexibility of the EcR ligand binding site. Several new non-steroidal chemical classes of ecdysone agonists, designed by guidance from protein X-ray studies, are described. |
| |
Keywords: | |
本文献已被 ScienceDirect 等数据库收录! |
|