Contacts:
Tel: 050 2219566
e-mail: rebecca.ferrisi@phd.unipi.it
Supervisors:
Professor Clementina Manera
PhD project Title:
Design, synthesis and biological evaluation of allosteric and bivalent ligands for novel strategies targeting G protein-coupled receptors
Research summary:
My PhD research project will focus on the following milestones:
- synthesis of allosteric ligands
- synthesis of bivalent ligands
Regarding allosteric modulators, they have become relevant in the last decade as a new strategy to overcome the classical side effects due to the direct modulation of the orthosteric binding site. The allosteric ligands are able to induce conformational changes, modifying ligand affinity, functional efficacy and functional potency. They present several advantages such as higher receptor subtype and tissue selectivity, effect saturability and biased signaling towards orthosteric ligands which engage certain signaling interactions rather than other.
Regarding bivalent ligands, I will focused on the synthesis of bitopic ligands, which simultaneously bind to the both allosteric and orthosteric site. This subclass of ligands exhibits the same advantages common to the allosteric ligands, but in addition provides a high affinity for the target GPCR and their effect occurs indipendently from the presence or absence of endogeneous tone.
The search of bivalent and allosteric ligands remains an important challenge also in relation to the endocannabinoid system. So, at the beginning, I’ll have a special consideration for this interesting research field.