Adenosine receptors are G protein-coupled receptors involved in important physio-pathological conditions. For this reason, from their discovery, the research of potent and selective ligands attracted the interest of researchers working in the field. Beyond the classical agonists, antagonists or allosteric ligands, several efforts were made in the development of functionalized ligands for the adenosine receptors. Functionalized ligands are molecules were an adenosine receptor ligand is conjugated to a moiety which confers new features to the molecule, such as additional therapeutic effect or target selectivity, receptor probing, improved pharmacokinetic profile, etc. In this commentary, an overview on the applications of functionalized ligands for the adenosine receptor was presented, even if most of the concepts are applicable to all G protein-coupled receptors.
