Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1361507 | Bioorganic & Medicinal Chemistry Letters | 2012 | 7 Pages |
Abstract
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 α7 and α4β2 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.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Ewald Edink, Atilla Akdemir, Chimed Jansen, René van Elk, Obbe Zuiderveld, Frans J.J. de Kanter, Jacqueline E. van Muijlwijk-Koezen, August B. Smit, Rob Leurs, Iwan J.P. de Esch,