Illuminating phenylazopyridines to photoswitch metabotropic glutamate receptors
Phenylazopyridines are photoisomerizable compounds with high potential to control biological functions with light. We have obtained a series of phenylazopyridines with light dependent activity as negative allosteric modulators (NAM) of metabotropic glutamate receptor subtype 5 (mGlu). Here we descri...
| Autores: | , , , , , , , , , , , , , |
|---|---|
| Tipo de documento: | artigo |
| Data de publicação: | 2017 |
| País: | España |
| Recursos: | Universitat Autònoma de Barcelona |
| Repositório: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglês |
| OAI Identifier: | oai:ddd.uab.cat:186140 |
| Acesso em linha: | https://ddd.uab.cat/record/186140 https://dx.doi.org/urn:doi:10.1021/acscentsci.6b00353 |
| Access Level: | Acceso aberto |
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Illuminating phenylazopyridines to photoswitch metabotropic glutamate receptorsfrom the flask to the animalsGómez-Santacana, Xavier|||0000-0001-8830-0494Pittolo, Silvia|||0000-0002-5673-1692Rovira, Xavier|||0000-0002-9764-9927Lopez, MarcZussy, CharleineDalton, James A. R.|||0000-0002-5279-4581Faucherre, AdèleJopling, ChrisPin, Jean-Philippe|||0000-0002-1423-345XCiruela, Francisco|||0000-0003-0832-3739Goudet, Cyril|||0000-0002-8255-3535Giraldo, Jesús|||0000-0001-7082-4695Gorostiza, Pau|||0000-0002-7268-5577Llebaria, Amadeu|||0000-0002-8200-4827Phenylazopyridines are photoisomerizable compounds with high potential to control biological functions with light. We have obtained a series of phenylazopyridines with light dependent activity as negative allosteric modulators (NAM) of metabotropic glutamate receptor subtype 5 (mGlu). Here we describe the factors needed to achieve an operational molecular photoisomerization and its effective translation into in vitro and in vivo receptor photoswitching, which includes zebrafish larva motility and the regulation of the antinociceptive effects in mice. The combination of light and some specific phenylazopyridine ligands displays atypical pharmacological profiles, including light-dependent receptor overactivation, which can be observed both in vitro and in vivo. Remarkably, the localized administration of light and a photoswitchable compound in the peripheral tissues of rodents or in the brain amygdalae results in an illumination-dependent analgesic effect. The results reveal a robust translation of the phenylazopyridine photoisomerization to a precise photoregulation of biological activity. The cis - trans photoisomerization of phenylazopyridines, allowing mGlu receptor activity photoswitching in cells, is used in vivo to control zebrafish motility with light and analgesia in mice including peripheral and brain localized illumination. 22017-01-0120172017-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/186140https://dx.doi.org/urn:doi:10.1021/acscentsci.6b00353reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 CTQ2014-57020-RMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 PCIN-2013-017-C03-01Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PIE14/00034Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2014-55700-PMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 PCIN-2013-019-C03-03Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2014-58396-RAgència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2010/BP-A00194Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2012/FI_B01122Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2012/CTP00033Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2012/BE100597Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-1251Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-00109open accesshttp://purl.org/coar/access_right/c_abf2Aquest material està protegit per drets d'autor i/o drets afins. Podeu utilitzar aquest material en funció del que permet la legislació de drets d'autor i drets afins d'aplicació al vostre cas. Per a d'altres usos heu d'obtenir permís del(s) titular(s) de drets.https://rightsstatements.org/vocab/InC/1.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1861402026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
Illuminating phenylazopyridines to photoswitch metabotropic glutamate receptors from the flask to the animals |
| title |
Illuminating phenylazopyridines to photoswitch metabotropic glutamate receptors |
| spellingShingle |
Illuminating phenylazopyridines to photoswitch metabotropic glutamate receptors Gómez-Santacana, Xavier|||0000-0001-8830-0494 |
| title_short |
Illuminating phenylazopyridines to photoswitch metabotropic glutamate receptors |
| title_full |
Illuminating phenylazopyridines to photoswitch metabotropic glutamate receptors |
| title_fullStr |
Illuminating phenylazopyridines to photoswitch metabotropic glutamate receptors |
| title_full_unstemmed |
Illuminating phenylazopyridines to photoswitch metabotropic glutamate receptors |
| title_sort |
Illuminating phenylazopyridines to photoswitch metabotropic glutamate receptors |
| dc.creator.none.fl_str_mv |
Gómez-Santacana, Xavier|||0000-0001-8830-0494 Pittolo, Silvia|||0000-0002-5673-1692 Rovira, Xavier|||0000-0002-9764-9927 Lopez, Marc Zussy, Charleine Dalton, James A. R.|||0000-0002-5279-4581 Faucherre, Adèle Jopling, Chris Pin, Jean-Philippe|||0000-0002-1423-345X Ciruela, Francisco|||0000-0003-0832-3739 Goudet, Cyril|||0000-0002-8255-3535 Giraldo, Jesús|||0000-0001-7082-4695 Gorostiza, Pau|||0000-0002-7268-5577 Llebaria, Amadeu|||0000-0002-8200-4827 |
| author |
Gómez-Santacana, Xavier|||0000-0001-8830-0494 |
| author_facet |
Gómez-Santacana, Xavier|||0000-0001-8830-0494 Pittolo, Silvia|||0000-0002-5673-1692 Rovira, Xavier|||0000-0002-9764-9927 Lopez, Marc Zussy, Charleine Dalton, James A. R.|||0000-0002-5279-4581 Faucherre, Adèle Jopling, Chris Pin, Jean-Philippe|||0000-0002-1423-345X Ciruela, Francisco|||0000-0003-0832-3739 Goudet, Cyril|||0000-0002-8255-3535 Giraldo, Jesús|||0000-0001-7082-4695 Gorostiza, Pau|||0000-0002-7268-5577 Llebaria, Amadeu|||0000-0002-8200-4827 |
| author_role |
author |
| author2 |
Pittolo, Silvia|||0000-0002-5673-1692 Rovira, Xavier|||0000-0002-9764-9927 Lopez, Marc Zussy, Charleine Dalton, James A. R.|||0000-0002-5279-4581 Faucherre, Adèle Jopling, Chris Pin, Jean-Philippe|||0000-0002-1423-345X Ciruela, Francisco|||0000-0003-0832-3739 Goudet, Cyril|||0000-0002-8255-3535 Giraldo, Jesús|||0000-0001-7082-4695 Gorostiza, Pau|||0000-0002-7268-5577 Llebaria, Amadeu|||0000-0002-8200-4827 |
| author2_role |
author author author author author author author author author author author author author |
| description |
Phenylazopyridines are photoisomerizable compounds with high potential to control biological functions with light. We have obtained a series of phenylazopyridines with light dependent activity as negative allosteric modulators (NAM) of metabotropic glutamate receptor subtype 5 (mGlu). Here we describe the factors needed to achieve an operational molecular photoisomerization and its effective translation into in vitro and in vivo receptor photoswitching, which includes zebrafish larva motility and the regulation of the antinociceptive effects in mice. The combination of light and some specific phenylazopyridine ligands displays atypical pharmacological profiles, including light-dependent receptor overactivation, which can be observed both in vitro and in vivo. Remarkably, the localized administration of light and a photoswitchable compound in the peripheral tissues of rodents or in the brain amygdalae results in an illumination-dependent analgesic effect. The results reveal a robust translation of the phenylazopyridine photoisomerization to a precise photoregulation of biological activity. The cis - trans photoisomerization of phenylazopyridines, allowing mGlu receptor activity photoswitching in cells, is used in vivo to control zebrafish motility with light and analgesia in mice including peripheral and brain localized illumination. |
| publishDate |
2017 |
| dc.date.none.fl_str_mv |
2 2017-01-01 2017 2017-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
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article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/186140 https://dx.doi.org/urn:doi:10.1021/acscentsci.6b00353 |
| url |
https://ddd.uab.cat/record/186140 https://dx.doi.org/urn:doi:10.1021/acscentsci.6b00353 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CTQ2014-57020-R Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PCIN-2013-017-C03-01 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PIE14/00034 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2014-55700-P Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PCIN-2013-019-C03-03 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2014-58396-R Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2010/BP-A00194 Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2012/FI_B01122 Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2012/CTP00033 Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2012/BE100597 Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-1251 Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-00109 |
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open access http://purl.org/coar/access_right/c_abf2 https://rightsstatements.org/vocab/InC/1.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://rightsstatements.org/vocab/InC/1.0/ |
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openAccess |
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application/pdf |
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