Computer-aided discovery of aromatic L-α-amino acids as agonists of the orphan G protein-coupled receptor GPR139

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Vignir Ísberg, Kirsten Bayer Andersen, Christoph Bisig, Gunnar Ph Dietz, Hans Bräuner-Osborne, David Erik Gloriam

GPR139 is an orphan G protein-coupled receptor expressed mainly in the central nervous system. We developed a pharmacophore model based on known GPR139 surrogate agonists which led us to propose aromatic-containing dipeptides as potential ligands. Upon testing, the dipeptides demonstrated agonism in the Gq pathway. Next, testing all 20 proteinogenic L-α-amino acids; L-tryptophan and L-phenylalanine were found to have EC50 values of 220 µM and 320 µM, respectively, making them the first putative endogenous agonists for GPR139.

Original languageEnglish
JournalJournal of Chemical Information and Modeling
Issue number6
Pages (from-to)1553-1557
Number of pages5
Publication statusPublished - 14 May 2014

ID: 112862682