Work from this international collaboration spanning Denmark, Italy, Sweden and the USA brings insights into the synthesis and characterization of a selective agonist for the metabotropic glutamate receptor mGluR2, a potential therapeutic target for neurologic and psychiatric diseases.
The team’s approach to the agonist design was to induce selectivity for mGluR2 over other family members via imposing conformational rigidity into the carbon skeleton of the Glu analogues. This resulted in an increase of selectivity of at least two orders of magnitude compared to homologous mGluR3 as well as mGluR1, 4, 5, 7.
A highly selective agonist for the metabotropic glutamate receptor mGluR2
Simon D. Nielsen, Marica Fulco, Michaela Serpi, Birgitte Nielsen, Maria B. Hansen, Kasper L. Hansen, Christian Thomsen, Robb Brodbeck, Hans Bräuner-Osborne, Roberto Pellicciari, Per-Ola Norrby, Jeremy R. Greenwood and Rasmus P. Clausen