dc.contributor.author |
Doornbos, Maarten L. J. |
dc.contributor.author |
Wang, Xuesong |
dc.contributor.author |
Vermond, Sophie C. |
dc.contributor.author |
Peeters, Luc |
dc.contributor.author |
Pérez-Benito, Laura |
dc.contributor.author |
Trabanco, Andrés A. |
dc.contributor.author |
Lavreysen, Hilde |
dc.contributor.author |
Cid, José María |
dc.contributor.author |
Heitman, Laura H. |
dc.contributor.author |
Tresadern, Gary |
dc.contributor.author |
IJzerman, Adriaan P. |
dc.date |
2018 |
dc.date.accessioned |
2022-10-28T12:27:48Z |
dc.date.available |
2022-10-28T12:27:48Z |
dc.date.issued |
2022-10-28 |
dc.identifier |
https://ddd.uab.cat/record/227899 |
dc.identifier |
urn:10.1021/acs.jmedchem.8b00051 |
dc.identifier |
urn:oai:ddd.uab.cat:227899 |
dc.identifier |
urn:pmid:29494768 |
dc.identifier |
urn:pmcid:PMC6331142 |
dc.identifier |
urn:pmc-uid:6331142 |
dc.identifier |
urn:articleid:15204804v62p223 |
dc.identifier |
urn:oai:pubmedcentral.nih.gov:6331142 |
dc.identifier |
urn:oai:egreta.uab.cat:publications/2a7663d1-288f-4991-b8e2-cbd8460b5e29 |
dc.identifier |
urn:scopus_id:85059815540 |
dc.identifier.uri |
http://hdl.handle.net/2072/523518 |
dc.format |
application/pdf |
dc.language |
eng |
dc.publisher |
|
dc.relation |
Journal of Medicinal Chemistry ; Vol. 62 (march 2018), p. 223-233 |
dc.rights |
open access |
dc.rights |
Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. |
dc.rights |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
dc.title |
Covalent Allosteric Probe for the Metabotropic Glutamate Receptor 2 : Design, Synthesis, and Pharmacological Characterization |
dc.type |
Article |
dc.description.abstract |
Covalent labeling of G protein-coupled receptors (GPCRs) by small molecules is a powerful approach to understand binding modes, mechanism of action, pharmacology, and even facilitate structure elucidation. We report the first covalent positive allosteric modulator (PAM) for a class C GPCR, the mGlu receptor. Three putatively covalent mGlu PAMs were designed and synthesized. Pharmacological characterization identified 2 to bind the receptor covalently. Computational modeling combined with receptor mutagenesis revealed T791 7.29×30 as the likely position of covalent interaction. We show how this covalent ligand can be used to characterize the PAM binding mode and that it is a valuable tool compound in studying receptor function and binding kinetics. Our findings advance the understanding of the mGlu PAM interaction and suggest that 2 is a valuable probe for further structural and chemical biology approaches. |