Acetylcholine binding protein (AChBP) as template for hierarchical in silico screening procedures to identify structurally novel ligands for the nicotinic receptors.
Bioorg Med Chem
; 19(20): 6107-19, 2011 Oct 15.
Article
en En
| MEDLINE
| ID: mdl-21920761
ABSTRACT
Hierarchical in silico screening protocols against the agonist bound acetylcholine binding protein (AChBP) crystal structure were efficient in identifying novel chemotypes for AChBP and the human α7 receptor. Two hit structures were cocrystallized with AChBP revealing intermolecular cation-π interactions with loop C but lacking intermolecular hydrogen bonding. The compounds act as competitive α7 receptor antagonists and as non-competitive α4ß2 receptor inhibitors. These results underline the usability of AChBP in structure-based in silico screening strategies in finding novel scaffolds for the α7 receptor, but also illustrates some limitations of using AChBP as bait to find competitive α4ß2 receptor ligands and α7 receptor agonists.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Portadoras
/
Receptores Nicotínicos
/
Antagonistas Nicotínicos
/
Agonistas Nicotínicos
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
/
Screening_studies
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Países Bajos