An allosteric modulator to control endogenous G protein-coupled receptors with light - PubMed (original) (raw)

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

Silvia Pittolo et al. Nat Chem Biol. 2014 Oct.

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.

PubMed Disclaimer

Similar articles

• Shining Light on an mGlu5 Photoswitchable NAM: A Theoretical Perspective.
  Dalton JA, Lans I, Rovira X, Malhaire F, Gómez-Santacana X, Pittolo S, Gorostiza P, Llebaria A, Goudet C, Pin JP, Giraldo J. Dalton JA, et al. Curr Neuropharmacol. 2016;14(5):441-54. doi: 10.2174/1570159x13666150407231417. Curr Neuropharmacol. 2016. PMID: 26391742 Free PMC article.
• Probe dependence and biased potentiation of metabotropic glutamate receptor 5 is mediated by differential ligand interactions in the common allosteric binding site.
  Hellyer SD, Sengmany K, Keller AN, Christopoulos A, Leach K, Gregory KJ. Hellyer SD, et al. Biochem Pharmacol. 2020 Jul;177:114013. doi: 10.1016/j.bcp.2020.114013. Epub 2020 May 8. Biochem Pharmacol. 2020. PMID: 32389635
• Differential contribution of metabotropic glutamate receptor 5 common allosteric binding site residues to biased allosteric agonism.
  Sengmany K, Hellyer SD, Christopoulos A, Lapinsky DJ, Leach K, Gregory KJ. Sengmany K, et al. Biochem Pharmacol. 2020 Jul;177:114011. doi: 10.1016/j.bcp.2020.114011. Epub 2020 May 5. Biochem Pharmacol. 2020. PMID: 32380090
• Structure-based discovery and development of metabotropic glutamate receptor 5 negative allosteric modulators.
  Bennett KA, Christopher JA, Tehan BG. Bennett KA, et al. Adv Pharmacol. 2020;88:35-58. doi: 10.1016/bs.apha.2020.03.001. Epub 2020 Mar 25. Adv Pharmacol. 2020. PMID: 32416871 Review.
• Metabotropic glutamate receptor subtype 5: molecular pharmacology, allosteric modulation and stimulus bias.
  Sengmany K, Gregory KJ. Sengmany K, et al. Br J Pharmacol. 2016 Oct;173(20):3001-17. doi: 10.1111/bph.13281. Epub 2015 Nov 11. Br J Pharmacol. 2016. PMID: 26276909 Free PMC article. Review.

Cited by

• Optogenetic Techniques for Manipulating and Sensing G Protein-Coupled Receptor Signaling.
  Abreu N, Levitz J. Abreu N, et al. Methods Mol Biol. 2020;2173:21-51. doi: 10.1007/978-1-0716-0755-8_2. Methods Mol Biol. 2020. PMID: 32651908 Free PMC article. Review.
• Photoswitchable positive allosteric modulators of metabotropic glutamate receptor 4 to improve selectivity.
  Panarello S, González-Díez A, Berizzi AE, Malhaire F, Borràs-Tudurí R, Rovira X, Serra C, Prézeau L, Pin JP, Goudet C, Llebaria A, Gómez-Santacana X. Panarello S, et al. iScience. 2024 May 28;27(6):110123. doi: 10.1016/j.isci.2024.110123. eCollection 2024 Jun 21. iScience. 2024. PMID: 38966572 Free PMC article.
• A Light-Controlled Allosteric Modulator Unveils a Role for mGlu4 Receptors During Early Stages of Ischemia in the Rodent Cerebellar Cortex.
  Bossi S, Helleringer R, Galante M, Monlleó E, Trapero A, Rovira X, Daniel H, Llebaria A, McLean H. Bossi S, et al. Front Cell Neurosci. 2018 Nov 27;12:449. doi: 10.3389/fncel.2018.00449. eCollection 2018. Front Cell Neurosci. 2018. PMID: 30542267 Free PMC article.
• Orthogonal Control of Neuronal Circuits and Behavior Using Photopharmacology.
  Castagna R, Kolarski D, Durand-de Cuttoli R, Maleeva G. Castagna R, et al. J Mol Neurosci. 2022 Jul;72(7):1433-1442. doi: 10.1007/s12031-022-02037-3. Epub 2022 Jun 23. J Mol Neurosci. 2022. PMID: 35737209 Review.
• Optical control of pain in vivo with a photoactive mGlu5 receptor negative allosteric modulator.
  Font J, López-Cano M, Notartomaso S, Scarselli P, Di Pietro P, Bresolí-Obach R, Battaglia G, Malhaire F, Rovira X, Catena J, Giraldo J, Pin JP, Fernández-Dueñas V, Goudet C, Nonell S, Nicoletti F, Llebaria A, Ciruela F. Font J, et al. Elife. 2017 Apr 11;6:e23545. doi: 10.7554/eLife.23545. Elife. 2017. PMID: 28395733 Free PMC article.

References

1. 1. Angew Chem Int Ed Engl. 2013 Jul 22;52(30):7704-8 - PubMed
2. 1. Proc Natl Acad Sci U S A. 1971 Aug;68(8):1820-3 - PubMed
3. 1. J Neurosci. 1995 Sep;15(9):6103-9 - PubMed
4. 1. Biochemistry. 2013 Dec 17;52(50):8972-4 - PubMed
5. 1. Br J Pharmacol. 2003 Mar;138(6):1026-30 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Nature Publishing Group

• Other Literature Sources

  • The Lens - Patent Citations Database
  • scite Smart Citations

• Molecular Biology Databases

  • Guide to Pharmacology