Molecular basis of agonist docking in a human GPR103 homology model by site-directed mutagenesis and structure-activity relationship studies

Cindy Neveu (1, 2) , Fabienne Dulin (3) , Benjamin Lefranc (2) , Ludovic Galas (2) , Colas Calbrix (2) , Ronan Bureau (3) , Sylvain Rault (3) , Julien Chuquet (1, 2) , Jean A Boutin (4) , Laure Guilhaudis (5) , Isabelle Ségalas-Milazzo (5) , David Vaudry (1, 2) , Hubert Vaudry (1, 2) , Jana Sopkova-de Oliveira Santos (3) , Jérôme Leprince (1, 2)

1 DC2N - Différenciation et communication neuronale et neuroendocrine
2 PRIMACEN - Plate-Forme de Recherche en Imagerie Cellulaire de Haute-Normandie
3 CERMN - Centre d'Etudes et de Recherche sur le Médicament de Normandie
4 IRIS - Institut de Recherches Internationales Servier [Suresnes]
5 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse

The neuropeptide 26RFa and its cognate receptor GPR103 are involved in the control of food intake and bone mineralization. Here, we have tested, experimentally, the predicted ligand-receptor interactions by site-directed mutagenesis of GPR103 and designed point-substituted 26RFa analogues.

Domains: Chemical Sciences; Medicinal Chemistry; Life Sciences [q-bio]; Cellular Biology; Cell Behavior [q-bio.CB]; Life Sciences [q-bio]; Neurons and Cognition [q-bio.NC]; Neurobiology; Life Sciences [q-bio]; Pharmaceutical sciences; Pharmacology

Cindy Neveu, Fabienne Dulin, Benjamin Lefranc, Ludovic Galas, Colas Calbrix, et al.. Molecular basis of agonist docking in a human GPR103 homology model by site-directed mutagenesis and structure-activity relationship studies. British Journal of Pharmacology, 2014, 171 (19), pp.4425-4439. ⟨10.1111/bph.12808⟩. ⟨hal-01973604⟩