Chemoproteomic Approach to Explore the Target Profile of GPCR ligands: Application to 5-HT1A and 5-HT6 Receptors

Gamo, Ana M.; González Vera, Juan Antonio; Rueda-Zubiaurre, Ainoa; Alonso, Dulce; Vázquez Villa, María Del Henar; Martín-Couce, Lidia; Palomares Gracia, Óscar; López, Juan A.; Martín-Fontecha Corrales, María Del Mar; Benhamú Salama, Bellinda; López-Rodríguez, María L.; Ortega Gutiérrez, Silvia

Chemoproteomic Approach to Explore the Target Profile of GPCR ligands: Application to 5-HT1A and 5-HT6 Receptors

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Official URL

https//doi.org/10.1002/chem.201503101

Publication date

2015

Publisher

Wiley

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URI

https://hdl.handle.net/20.500.14352/34961

Citation

Gamo, Ana M., Gónzalez-Vera, J. A., Rueda-Zubiaurre, A. et al. «Chemoproteomic Approach to Explore the Target Profile of GPCR Ligands: Application to 5‐HT 1A and 5‐HT 6 Receptors». Chemistry – A European Journal, vol. 22, n.o 4, enero de 2016, pp. 1313-21. DOI.org (Crossref), https://doi.org/10.1002/chem.201503101.

Abstract

Determination of the targets of a compound remains an essential aspect in drug discovery. A complete understanding of all binding interactions is critical to recognize in advance both therapeutic effects and undesired consequences. However, the complete polypharmacology of many drugs currently in clinical development is still unknown, especially in the case of G-protein-coupled receptor (GPCR) ligands. In this work we have developed a chemoproteomic platform based on the use of chemical probes to explore the target profile of a compound in biological systems. As proof of concept, this methodology has been applied to selected ligands of the therapeutically relevant serotonin 5-HT1A and 5-HT6 receptors, and we have identified and validated some of their off-targets. This approach could be extended to other drugs of interest to study the targeted proteome in disease-relevant systems.