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Summary:

G protein-coupled receptors (GPCRs) represent the largest family of signal-transducing molecules known. They convey signals for light and many extracellular regulatory molecules. GPCRs have been found to be dysfunctional/dysregulated in a growing number of human diseases and have been estimated to be the targets of more than 40% of the drugs used in clinical medicine today. The crystal structure of rhodopsin provides the first three-dimensional GPCR information, which now supports homology modeling studies and structure-based drug design approaches. Our scientific efforts are directed on adenosine receptors, a family of GPCRs and, in particular, on A₃ adenosine receptor subtype antagonists. We will place the greatest emphasis on an iterative, bi-directional approach in which models are used to generate hypotheses that are tested by experimentation and the experimental findings are, in turn, used to refine the model. The success of this approach is due to the synergistic interaction between theory and experiment.

Selected References:

 S. Moro, F. Deflorian, M. Bacilieri, G. Spalluto “G protein-coupled receptors as challenging druggable targets: insights from in silico studies.” New J. Chem. 30, 301-308 (2006)

 S. Moro, G. Spalluto, Z.-G. Gao, K. A. Jacobson “Progress in the pursuit of therapeutic adenosine receptor antagonists.” Med. Res. Rev. 26, 131-159 (2006)

 S. Moro, G. Spalluto, K. A. Jacobson “Recent development on computer aided engineering of GPCR ligands: the human A3 adenosine receptors as an example.” Trends Pharmacol. Sci. 26, 44-51 (2005)