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. 2007 Nov 5;35(2):389–396. doi: 10.1007/s00726-007-0604-2

Computational studies of the binding modes of A2A adenosine receptor antagonists

Y Ye 1, J Wei 1, X Dai 2, Q Gao 2
PMCID: PMC7087644  PMID: 17978889

Summary.

A molecular docking study was performed on several structurally diverse A2A AR antagonists, including xanthines, and non-xanthine type antagonists to investigate their binding modes with A2A adenosine receptor (AR), one of the four subtypes of AR, which is currently of great interest as a target for therapeutic intervention, in particular for Parkinson’s disease. The high-affinity binding site was found to be a hydrophobic pocket with the involvement of hydrogen bonding interactions as well as π–π stacking interactions with the ligands. The detailed binding modes for both xanthine and non-xanthine type A2A antagonists were compared and the essential features were extracted and converted to database searchable queries for virtual screening study of novel A2A AR antagonists. Findings from this study are helpful for elucidating the binding pattern of A2A AR antagonists and for the design of novel active ligands.

Keywords: Keywords: Adenosine receptors – A2A AR antagonists – Binding mode – Docking – Pharmacophore – Virtual screening

Footnotes

Authors’ address: Qingzhi Gao, Chemistry Department, XenoPort Inc., 3410 Central Expressway, Santa Clara, CA 95051, U.S.A.

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