A Comparison in the Use of the Crystallographic Structure of the Human A(1) or the A(2A) Adenosine Receptors as a Template for the Construction of a Homology Model of the A(3) Subtype

In the last decades, the field of therapeutic application in targeting the human A 3 adenosine receptor has represented a rapidly growing area of research in adenosine field. Both agonists and antagonists have been described to have a potential application in the treatment of several diseases, including, for example, glaucoma, cancer, and autoimmune inflammations. To date, the most severe factor limiting the accuracy of the structure-based molecular modeling approaches is the fact that the three-dimensional human A 3 structure has not yet been solved. However, the crystallographic structures of either human A 1 or A A javax.xml.bind.JAXBElement@20e7aedf subtypes are available as potential templates for the construction of its homologymodel. In this study, we have compared the propensity of bothmodels to accommodate a series of known potent and selective human A 3 agonists and antagonists. As described, on the basis of the results obtained from this preliminary study, it is possible to affirm that the human A 3 receptor model based on the crystallographic structure of the A 1 subtype can represent a valid alternative to the one conventionally used today, based on the available AA 2A structures.