Abstract
Acetylcholine binding protein (AChBP) is widely considered as a functional and structural homologue of the ligand binding domain of Cys-loop receptors. We report the use of AChBP as template to identify ligands for the nicotinic receptors (nAChRs). An in silico screening protocol was set up and applied to crystal structures of AChBP. Several ligands containing a dibenzosuberyl moiety were identified and shown to bind with high affinity to AChBP and α7 nAChRs. Two high affinity ligands were cocrystallized with AChBP, revealing the binding mode in the orthosteric site. Functional studies revealed that these two ligands caused inhibition of the α7, α4β2, and 5HT
Original language | English |
---|---|
Pages (from-to) | 2372-2383 |
Number of pages | 11 |
Journal | Journal of Medicinal Chemistry |
Volume | 52 |
DOIs | |
Publication status | Published - 2009 |