【文章名】Structure-based design, synthesis and structure-activity relationships of dibenzosuberyl- and benzoate-substituted tropines as ligands for acetylcholine-binding protein
Structure-based design, synthesis and structure-activity relationships of dibenzosuberyl- and benzoate-substituted tropines as ligands for acetylcholine-binding protein
作者
Edink, E; Akdemir, A; Jansen, C; van Elk, R; Zuiderveld, O; de Kanter, FJJ; van Muijlwijk-Koezen, JE; Smit, AB; Leurs, R; de Esch, IJP
[摘要]：Using structure-based optimization procedures on in silico hits, dibenzosuberyl- and benzoate substituted tropines were designed as ligands for acetylcholine-binding protein (AChBP). This protein is a homolog to the ligand binding domain of the nicotinic acetylcholine receptor (nAChR). Distinct SAR is observed between two AChBP species variants and between the alpha 7 and alpha 4 beta 2 nAChR subtype. The AChBP species differences are indicative of a difference in accessibility of a ligand-inducible subpocket. Hereby, we have identified a region that can be scrutinized to achieve selectivity for nicotinic receptor subtypes. (C) 2011 Elsevier Ltd. All rights reserved.
