Design, synthesis and characterization of a new series of fluorescent metabotropic glutamate receptor type 5 negative allosteric modulators

In recent years, new drug discovery approaches based on novel pharmacological concepts have emerged. Allosteric modulators, for example, target receptors at sites other than the orthosteric binding sites and can modulate agonist-mediated activation. Interestingly, allosteric regulation may allow a f...

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Autores: Fernández Dueñas, Víctor, Qian, Mingcheng, Argerich, Josep, Amaral, Carolina, Risseeuw, Martijn D.P., Van Calenbergh, Serge, Ciruela Alférez, Francisco
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/161893
Acceso en línea:https://hdl.handle.net/2445/161893
Access Level:acceso abierto
Palabra clave:Enzims al·lostèrics
Nanomedicina
Lligands
Allosteric enzymes
Nanomedicine
Ligands
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spelling Design, synthesis and characterization of a new series of fluorescent metabotropic glutamate receptor type 5 negative allosteric modulatorsFernández Dueñas, VíctorQian, MingchengArgerich, JosepAmaral, CarolinaRisseeuw, Martijn D.P.Van Calenbergh, SergeCiruela Alférez, FranciscoEnzims al·lostèricsNanomedicinaLligandsAllosteric enzymesNanomedicineLigandsIn recent years, new drug discovery approaches based on novel pharmacological concepts have emerged. Allosteric modulators, for example, target receptors at sites other than the orthosteric binding sites and can modulate agonist-mediated activation. Interestingly, allosteric regulation may allow a fine-tuned regulation of unbalanced neurotransmitter' systems, thus providing safe and effective treatments for a number of central nervous system diseases. The metabotropic glutamate type 5 receptor (mGlu5R) has been shown to possess a druggable allosteric binding domain. Accordingly, novel allosteric ligands are being explored in order to finely regulate glutamate neurotransmission, especially in the brain. However, before testing the activity of these new ligands in the clinic or even in animal disease models, it is common to characterize their ability to bind mGlu5Rs in vitro. Here, we have developed a new series of fluorescent ligands that, when used in a new NanoBRET-based binding assay, will facilitate screening for novel mGlu5R allosteric modulators.MDPI2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/161893Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3390/molecules25071532Molecules, 2020, vol. 25, num. 7, p. 1532https://doi.org/10.3390/molecules25071532cc-by (c) Fernández Dueñas, Víctor et al., 2020http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1618932026-05-27T06:46:51Z
dc.title.none.fl_str_mv Design, synthesis and characterization of a new series of fluorescent metabotropic glutamate receptor type 5 negative allosteric modulators
title Design, synthesis and characterization of a new series of fluorescent metabotropic glutamate receptor type 5 negative allosteric modulators
spellingShingle Design, synthesis and characterization of a new series of fluorescent metabotropic glutamate receptor type 5 negative allosteric modulators
Fernández Dueñas, Víctor
Enzims al·lostèrics
Nanomedicina
Lligands
Allosteric enzymes
Nanomedicine
Ligands
title_short Design, synthesis and characterization of a new series of fluorescent metabotropic glutamate receptor type 5 negative allosteric modulators
title_full Design, synthesis and characterization of a new series of fluorescent metabotropic glutamate receptor type 5 negative allosteric modulators
title_fullStr Design, synthesis and characterization of a new series of fluorescent metabotropic glutamate receptor type 5 negative allosteric modulators
title_full_unstemmed Design, synthesis and characterization of a new series of fluorescent metabotropic glutamate receptor type 5 negative allosteric modulators
title_sort Design, synthesis and characterization of a new series of fluorescent metabotropic glutamate receptor type 5 negative allosteric modulators
dc.creator.none.fl_str_mv Fernández Dueñas, Víctor
Qian, Mingcheng
Argerich, Josep
Amaral, Carolina
Risseeuw, Martijn D.P.
Van Calenbergh, Serge
Ciruela Alférez, Francisco
author Fernández Dueñas, Víctor
author_facet Fernández Dueñas, Víctor
Qian, Mingcheng
Argerich, Josep
Amaral, Carolina
Risseeuw, Martijn D.P.
Van Calenbergh, Serge
Ciruela Alférez, Francisco
author_role author
author2 Qian, Mingcheng
Argerich, Josep
Amaral, Carolina
Risseeuw, Martijn D.P.
Van Calenbergh, Serge
Ciruela Alférez, Francisco
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Enzims al·lostèrics
Nanomedicina
Lligands
Allosteric enzymes
Nanomedicine
Ligands
topic Enzims al·lostèrics
Nanomedicina
Lligands
Allosteric enzymes
Nanomedicine
Ligands
description In recent years, new drug discovery approaches based on novel pharmacological concepts have emerged. Allosteric modulators, for example, target receptors at sites other than the orthosteric binding sites and can modulate agonist-mediated activation. Interestingly, allosteric regulation may allow a fine-tuned regulation of unbalanced neurotransmitter' systems, thus providing safe and effective treatments for a number of central nervous system diseases. The metabotropic glutamate type 5 receptor (mGlu5R) has been shown to possess a druggable allosteric binding domain. Accordingly, novel allosteric ligands are being explored in order to finely regulate glutamate neurotransmission, especially in the brain. However, before testing the activity of these new ligands in the clinic or even in animal disease models, it is common to characterize their ability to bind mGlu5Rs in vitro. Here, we have developed a new series of fluorescent ligands that, when used in a new NanoBRET-based binding assay, will facilitate screening for novel mGlu5R allosteric modulators.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/161893
url https://hdl.handle.net/2445/161893
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/molecules25071532
Molecules, 2020, vol. 25, num. 7, p. 1532
https://doi.org/10.3390/molecules25071532
dc.rights.none.fl_str_mv cc-by (c) Fernández Dueñas, Víctor et al., 2020
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Fernández Dueñas, Víctor et al., 2020
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Patologia i Terapèutica Experimental)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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