title: Adenosine receptor modelling. A1/A2a selectivity.
abstract: Three-dimensional models of the A(1) and A(2a) adenosine receptors (AR) were constructed by means of a homology procedure, using bovine rhodopsin as a template. In order to validate the two models, a docking analysis of selective agonists was carried out. The study shows that A(1)/A(2a) selectivity is mainly influenced by the different ability of the two receptors to give lipophilic interactions, instead of giving different H bonds. The binding site cavity of the A(1)AR is smaller than that of the A(2a)AR, and for this reason, less bulky ligands like CPA are able to give close interactions with the A(1)AR, unlike larger ligands such as CGS-21680. The different dimensions of the binding site cavity could be due to the presence of three residues of proline, which cause a different rearrangement of the TM, thus modifying the side chain disposition inside the inter-helix channel.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Pisa, Italy.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Tuccinardi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ortore
authors.forename: Clementina
authors.initials: C
authors.lastname: Manera
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saccomanni
authors.forename: Adriano
authors.initials: A
authors.lastname: Martinelli
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists; D058908:Adenosine A2 Receptor Agonists; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D003198:Computer Simulation; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010627:Phenethylamines / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D016415:Sequence Alignment
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058908:Adenosine A2 Receptor Agonists; D008024:Ligands; D010627:Phenethylamines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000241:Adenosine