An allosteric modulator to control endogenous G protein-coupled receptors with light

Silvia Pittolo; Xavier Gómez-Santacana; Kay Eckelt; Xavier Rovira; James Dalton; Cyril Goudet; Jean-Philippe Pin; Artur Llobet; Jesús Giraldo; Amadeu Llebaria; Pau Gorostiza

doi:10.1038/nchembio.1612

An allosteric modulator to control endogenous G protein-coupled receptors with light

Nat Chem Biol. 2014 Oct;10(10):813-5. doi: 10.1038/nchembio.1612. Epub 2014 Aug 31.

Authors

Affiliations

¹ 1] Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain. [2].
² 1] Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain. [2] Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona, Spain. [3] Institut de Neurociències and Unitat de Bioestadística, Universitat Autònoma de Barcelona, Bellaterra, Spain. [4].
³ 1] Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain. [2] Network Biomedical Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Zaragoza, Spain.
⁴ 1] Institut de Neurociències and Unitat de Bioestadística, Universitat Autònoma de Barcelona, Bellaterra, Spain. [2] Institut de Génomique Fonctionnelle, CNRS, UMR-5203, Université de Montpellier, Montpellier, France. [3] INSERM, U661, F-34000 Montpellier, France.
⁵ Institut de Neurociències and Unitat de Bioestadística, Universitat Autònoma de Barcelona, Bellaterra, Spain.
⁶ 1] Institut de Génomique Fonctionnelle, CNRS, UMR-5203, Université de Montpellier, Montpellier, France. [2] INSERM, U661, F-34000 Montpellier, France.
⁷ Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
⁸ 1] Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona, Spain. [2].
⁹ 1] Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain. [2] Network Biomedical Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Zaragoza, Spain. [3] Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain. [4].

PMID: 25173999
DOI: 10.1038/nchembio.1612

Abstract

Controlling drug activity with light offers the possibility of enhancing pharmacological selectivity with spatial and temporal regulation, thus enabling highly localized therapeutic effects and precise dosing patterns. Here we report on the development and characterization of what is to our knowledge the first photoswitchable allosteric modulator of a G protein-coupled receptor. Alloswitch-1 is selective for the metabotropic glutamate receptor mGlu5 and enables the optical control of endogenous mGlu5 receptors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Allosteric Regulation / radiation effects
Allosteric Site
Animals
Animals, Newborn
Astrocytes / cytology
Astrocytes / drug effects
Astrocytes / metabolism
Astrocytes / radiation effects
Azo Compounds / chemistry*
Gene Expression
HEK293 Cells
Humans
Larva / drug effects
Larva / physiology
Larva / radiation effects
Light
Photochemical Processes
Primary Cell Culture
Pyridines / chemical synthesis
Pyridines / pharmacology*
Rats
Receptor, Metabotropic Glutamate 5 / agonists
Receptor, Metabotropic Glutamate 5 / antagonists & inhibitors
Receptor, Metabotropic Glutamate 5 / genetics
Receptor, Metabotropic Glutamate 5 / metabolism*
Recombinant Proteins / chemistry
Recombinant Proteins / genetics
Transfection
Xenopus / physiology

Substances

Azo Compounds
Grm5 protein, rat
Pyridines
Receptor, Metabotropic Glutamate 5
Recombinant Proteins
azobenzene

Associated data

PubChem-Substance/196409788
PubChem-Substance/196409789
PubChem-Substance/196409790
PubChem-Substance/196409791
PubChem-Substance/196409792
PubChem-Substance/196409793
PubChem-Substance/196409794
PubChem-Substance/196409795
PubChem-Substance/196409796
PubChem-Substance/196409797
PubChem-Substance/196409798
PubChem-Substance/196409799
PubChem-Substance/196409800
PubChem-Substance/196409801