Adenosine A2A receptor agonists: CoMFA-based selection of the most predictive conformation.
A step-wise comparative molecular field analysis (CoMFA)-based procedure was applied to a series of 51 2-oxyadenosines in order to select the most predictive conformation for binding to A2A adenosine receptor (AR). The highest correlation and predictive power were found for conformers with side chain at 2nd position oriented in the direction opposite to the exocyclic amino group on the adenine ring (torsion N1C2OR = 120 degrees) and fully extended. The interaction of ligand and receptor is under steric and electrostatic control. The steric contribution is of a greater importance for the predictivity than the electrostatic one. Hydrophobicity of the compounds investigated does not affect significantly either the affinity to A2A AR, nor the predictivity of the models.
Doytchinova
I
I
Department of Chemistry, Faculty of Pharmacy, Medical University-Sofia, Bulgaria. irini.doytchinova@jenner.ac.uk
Valkova
I
I
Natcheva
R
R
D000241:Adenosine / Q000737:chemistry* / Q000502:physiology; D005544:Forecasting; D006801:Humans; D008024:Ligands; D008956:Models, Chemical; D008968:Molecular Conformation; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000737:chemistry; D012995:Solubility
D008024:Ligands; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D000241:Adenosine