IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
An heterobifunctional probe with allosteric properties on the nicotínic acetylcholine receptor.
Autor/es:
PAVáN, CARLOS; DEL CANTO, SERGIO; BISCOGLIO, MIRTHA JOSEFA
Lugar:
Huerta Grande, Córdoba
Reunión:
Congreso; XXVIII Reunion Anual de la Sociedad Argentina de Investigacion en Neurociencias; 2013
Institución organizadora:
Sociedad Argentina de Investigación en Neurociencias
Resumen:
An heterobifunctional probe (AC4-ASA) was developed as a tool for the study of cholinergic receptor binding sites. Acetylcholine was derivatized at its alkyl end and, through a short spacer, with a photoactivatable aryl-azide group. The probe was able to specifically interact with the muscle nicotinic receptor  and has a considerable selectivity for its α/δ binding site. This ligand showed the capability of modyfing the affininty of (-)-[3H]-nicotine for the muscle-type nicotinic receptor through, at least, one new allosteric binding site, different from the typical orthosteric binding sites. A detailed study of in-gel digestion of alpha and delta subunits followed by mass spectrometry was carried out with the objective of delineating such binding site. Moreover, automated docking studies were performed between AC4-ASA and the crystal structure of the                                                                                                                          nicotinic acethylcholine receptor from Torpedo californica. Results obtained, taken as a whole, allowed us to suggest the localization and structural aspects of the allosteric binding site.