9/2/2015

Thesis defence of María Martí: “Ligand selectivity at GPCRS: from multi-target binding profiles to biased agonism”

On 10^rd of February, María Martí, member of the PharmacoInformatics group of GRIB (IMIM-UPF) will defend her thesis at 11:00 at Josep Marull Room (QMAR building). You are all invited to this event.

Abstract:

Deeper characterization of drugs targeting G protein-coupled receptors (GPCR)s has shown that their mechanisms of action can be more complex than previously thought. On the one hand, binding affinity analyses towards a panel of related receptors have revealed that most drugs have affinity for multiple targets. On the other, characterization of drug efficacy for different receptor pathways has made evident that some ligands can selectively activate particular pathways, thus acting as biased agonists. In this work, we used models derived from new experimental data on receptor 3D structure and pharmacology to rationalize the structural determinants of multi-target affinity and biased agonism for different GPCR ligands. This insight can help obtain new molecular probes to assess the importance of specific affinity and efficacy profiles for the treatment of complex diseases such as schizophrenia. Furthermore, it can set the basis for the rational design of new ligands exploiting different forms of selectivity and capable of separating therapeutic effects from side effects.