Computer-Aided Discovery of Aromatic l‑α-Amino Acids as Agonists of the Orphan G Protein-Coupled Receptor GPR139
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...
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| Veröffentlicht in: | Journal of chemical information and modeling 2014-06, Vol.54 (6), p.1553-1557 |
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| container_end_page | 1557 |
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| container_issue | 6 |
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| container_title | Journal of chemical information and modeling |
| container_volume | 54 |
| creator | Isberg, Vignir Andersen, Kirsten B Bisig, Christoph Dietz, Gunnar P. H Bräuner-Osborne, Hans Gloriam, David E |
| description | 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, in testing all 20 proteinogenic l-α-amino acids, L-tryptophan and l-phenylalanine were found to have EC50 values of 220 and 320 μM, respectively, making them the first putative endogenous agonists for GPR139. |
| doi_str_mv | 10.1021/ci500197a |
| format | Article |
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| fulltext | fulltext |
| identifier | ISSN: 1549-9596 |
| ispartof | Journal of chemical information and modeling, 2014-06, Vol.54 (6), p.1553-1557 |
| issn | 1549-9596 1549-960X |
| language | eng |
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| source | MEDLINE; ACS Publications |
| subjects | Amino Acids, Aromatic - chemistry Amino Acids, Aromatic - pharmacology Computer-Aided Design Dipeptides - chemistry Dipeptides - pharmacology Drug Design HEK293 Cells Humans Models, Molecular Nerve Tissue Proteins - agonists Nerve Tissue Proteins - metabolism Phenylalanine - chemistry Phenylalanine - pharmacology Receptors, G-Protein-Coupled - agonists Receptors, G-Protein-Coupled - metabolism Tryptophan - chemistry Tryptophan - pharmacology |
| title | Computer-Aided Discovery of Aromatic l‑α-Amino Acids as Agonists of the Orphan G Protein-Coupled Receptor GPR139 |
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