Stereospecific Inhibition of Ethanol Potentiation on Glycine Receptor by M554 Stereoisomers

Pilar A. Vásquez, Loreto San Martín, Yenifer Argel, Camila Riquelme, Josefa Torres, Felipe Vidal, Francisca Cayuman, Patricio Castro, Jorge Fuentealba, Gustavo Moraga-Cid, Gonzalo Yevenes, Chunyang Jin, Verónica A. Jiménez, Leonardo Guzmán

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

Resumen

Blocking the interaction between the Gβγprotein and the glycine receptor (GlyR) has emerged as a promising pharmacological strategy to treat acute alcohol intoxication by inhibiting ethanol potentiation on GlyR. M554 is a recently discovered small molecule capable of binding to Gβγwith potent in vitro and in vivo inhibitory activity. This compound has been tested as a mixture of diastereomers, and no information is available concerning the stereospecific activity of each species, which is critical to pursue efforts on lead optimization and drug development. In this work, we explored the differential activity of four M554 stereoisomers by in silico molecular dynamics simulations and electrophysiological experiments. Our results revealed that the (R,R)-M554 stereoisomer is a promising lead compound that inhibits ethanol potentiation of GlyR.

Idioma originalInglés
PublicaciónJournal of Chemical Information and Modeling
DOI
EstadoEn prensa - 2020

Áreas temáticas de ASJC Scopus

  • Química (todo)
  • Ingeniería química (todo)
  • Informática aplicada
  • Biblioteconomía y ciencias de la información

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