Nuevo ligando con acción alostérica sobre el receptor nicotínico de Torpedo californica
The nicotinic acetylcholine receptor belongs to a superfamily of ion channel receptors\ntriggered by ligand, also known as cystine-loop receptors. It is widely distributed in\nnature; in mammalian the neuronal subtype is present at the cholinergic synapses of the\nperipheral and central nervous syst...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2019
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_2960 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_2960.dir/2960.PDF |
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I28-R145-HWA_2960 |
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I28-R145-HWA_29602020-07-05 �� The nicotinic acetylcholine receptor belongs to a superfamily of ion channel receptors\ntriggered by ligand, also known as cystine-loop receptors. It is widely distributed in\nnature; in mammalian the neuronal subtype is present at the cholinergic synapses of the\nperipheral and central nervous systems whereas muscle subtype is located at the\nneuromuscular junction. Alterations in nicotinic receptor subtypes cause a variety of\npathologies in humans: myasthenia gravis, Alzheimer's disease, certain types of epilepsy,\netc. Currently, there are no drugs which are allosteric modulators of the receptor and\nused in therapeutics.\nIn this work we studied its interaction with a ligand called AC4-ASA, with properties\nof allosteric modulator of the nicotinic receptor, in order to establish its binding\ndeterminants. We used the photo-affinity labeling strategy, followed by a mass\nspectrometry study.\nAC4-ASA binds to two sites at the ?/? interface, one site in ?/? and two other sites\nlocated on the ? subunit. We propose binding models for the interaction sites with the\nreceptor, as well as a possible mechanism of modulation of receptor affinity for nicotine. Fil: Paván, Carlos Humberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Buenos Aires, Argentina Facultad de Farmacia y Bioquímica Biscoglio de Jiménez Bonino, Mirtha Paván, Carlos Humberto 2019-05-10 El receptor nicotínico es un receptor ionotrópico de la superfamilia de canales iónicos\ngatillados por ligando, ampliamente distribuido en la naturaleza. En los mamíferos el\nsubtipo neuronal está presente en las sinapsis colinérgicas del sistema nervioso central y\ndel periférico mientras que el subtipo muscular se encuentra en la placa neuromuscular.\nLas alteraciones del receptor nicotínico ocasionan una amplia variedad de patologías:\nmiastenia gravis, enfermedad de Alzheimer, epilepsia, etc. Actualmente no se dispone\nde drogas con propiedades de modulación alostérica sobre este receptor útiles en\ntratamientos farmacológicos.\nEl presente trabajo estudia su interacción con un ligando que tiene propiedades de\nmodulador alostérico para el receptor nicotínico, denominado AC4-ASA; para ello, se\nutilizó la estrategia de marcación por fotoafinidad seguida de espectrometría de masas;\ncomplementariamente, se modeló su interacción mediante docking molecular.\nSe encontró que el AC4-ASA se une a un sitio en la interfase ?/?, a dos en la ?/? y a\notros dos sitios sobre ?, de modo que el ligando posee más de un sitio de interacción y se\nconfirma su capacidad de unión al sitio ortostérico. Del análisis de los sitios de unión se\npropone un mecanismo de modulación de la afinidad por la nicotina. application/pdf Miranda, María Victoria Calvo, Juan Carlos Ermácora, Mario Receptor nicotínico Modulación alostérica Nicotina Miastemia gravis Alzheirmer Epilepsia Tratamiento farmacológico Nicotinic acetycholine Allosteric modulators Nicotine Myasthenia gravis Alzheimer's disease Certain types de epilepsy spa Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ Ciencias de la vida Nuevo ligando con acción alostérica sobre el receptor nicotínico de Torpedo californica info:eu-repo/semantics/doctoralThesis info:ar-repo/semantics/tesis doctoral info:eu-repo/semantics/acceptedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_2960 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_2960.dir/2960.PDF |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-145 |
| collection |
Repositorio Digital de la Universidad de Buenos Aires (UBA) |
| language |
Español |
| orig_language_str_mv |
spa |
| topic |
�� Receptor nicotínico Modulación alostérica Nicotina Miastemia gravis Alzheirmer Epilepsia Tratamiento farmacológico Nicotinic acetycholine Allosteric modulators Nicotine Myasthenia gravis Alzheimer's disease Certain types de epilepsy Ciencias de la vida |
| spellingShingle |
�� Receptor nicotínico Modulación alostérica Nicotina Miastemia gravis Alzheirmer Epilepsia Tratamiento farmacológico Nicotinic acetycholine Allosteric modulators Nicotine Myasthenia gravis Alzheimer's disease Certain types de epilepsy Ciencias de la vida Paván, Carlos Humberto Nuevo ligando con acción alostérica sobre el receptor nicotínico de Torpedo californica |
| topic_facet |
�� Receptor nicotínico Modulación alostérica Nicotina Miastemia gravis Alzheirmer Epilepsia Tratamiento farmacológico Nicotinic acetycholine Allosteric modulators Nicotine Myasthenia gravis Alzheimer's disease Certain types de epilepsy Ciencias de la vida |
| description |
The nicotinic acetylcholine receptor belongs to a superfamily of ion channel receptors\ntriggered by ligand, also known as cystine-loop receptors. It is widely distributed in\nnature; in mammalian the neuronal subtype is present at the cholinergic synapses of the\nperipheral and central nervous systems whereas muscle subtype is located at the\nneuromuscular junction. Alterations in nicotinic receptor subtypes cause a variety of\npathologies in humans: myasthenia gravis, Alzheimer's disease, certain types of epilepsy,\netc. Currently, there are no drugs which are allosteric modulators of the receptor and\nused in therapeutics.\nIn this work we studied its interaction with a ligand called AC4-ASA, with properties\nof allosteric modulator of the nicotinic receptor, in order to establish its binding\ndeterminants. We used the photo-affinity labeling strategy, followed by a mass\nspectrometry study.\nAC4-ASA binds to two sites at the ?/? interface, one site in ?/? and two other sites\nlocated on the ? subunit. We propose binding models for the interaction sites with the\nreceptor, as well as a possible mechanism of modulation of receptor affinity for nicotine. |
| author2 |
Biscoglio de Jiménez Bonino, Mirtha |
| author_facet |
Biscoglio de Jiménez Bonino, Mirtha Paván, Carlos Humberto |
| format |
Tesis doctoral Tesis doctoral acceptedVersion |
| author |
Paván, Carlos Humberto |
| author_sort |
Paván, Carlos Humberto |
| title |
Nuevo ligando con acción alostérica sobre el receptor nicotínico de Torpedo californica |
| title_short |
Nuevo ligando con acción alostérica sobre el receptor nicotínico de Torpedo californica |
| title_full |
Nuevo ligando con acción alostérica sobre el receptor nicotínico de Torpedo californica |
| title_fullStr |
Nuevo ligando con acción alostérica sobre el receptor nicotínico de Torpedo californica |
| title_full_unstemmed |
Nuevo ligando con acción alostérica sobre el receptor nicotínico de Torpedo californica |
| title_sort |
nuevo ligando con acción alostérica sobre el receptor nicotínico de torpedo californica |
| publisher |
Facultad de Farmacia y Bioquímica |
| publishDate |
2019 |
| url |
http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_2960 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_2960.dir/2960.PDF |
| work_keys_str_mv |
AT pavancarloshumberto nuevoligandoconaccionalostericasobreelreceptornicotinicodetorpedocalifornica |
| _version_ |
1766017523090718720 |