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

TY - JOUR

T1 - Computer-aided discovery of aromatic L-α-amino acids as agonists of the orphan G protein-coupled receptor GPR139

AU - Ísberg, Vignir

AU - Andersen, Kirsten Bayer

AU - Bisig, Christoph

AU - Dietz, Gunnar Ph

AU - Bräuner-Osborne, Hans

AU - Gloriam, David Erik

PY - 2014/6/23

Y1 - 2014/6/23

N2 - 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.

AB - 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.

U2 - 10.1021/ci500197a

DO - 10.1021/ci500197a

M3 - Journal article

C2 - 24826842

SN - 1549-9596

VL - 54

SP - 1553

EP - 1557

JO - Journal of Chemical Information and Modeling

JF - Journal of Chemical Information and Modeling

IS - 6

ER -