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Structural Probing and Molecular Modeling of the A₃ Adenosine Receptor: A Focus on Agonist Binding.
- Source :
-
Molecules (Basel, Switzerland) [Molecules] 2017 Mar 11; Vol. 22 (3). Date of Electronic Publication: 2017 Mar 11. - Publication Year :
- 2017
-
Abstract
- Adenosine is an endogenous modulator exerting its functions through the activation of four adenosine receptor (AR) subtypes, termed A₁, A <subscript>2A</subscript> , A <subscript>2B</subscript> and A₃, which belong to the G protein-coupled receptor (GPCR) superfamily. The human A₃AR (hA₃AR) subtype is implicated in several cytoprotective functions. Therefore, hA₃AR modulators, and in particular agonists, are sought for their potential application as anti-inflammatory, anticancer, and cardioprotective agents. Structure-based molecular modeling techniques have been applied over the years to rationalize the structure-activity relationships (SARs) of newly emerged A₃AR ligands, guide the subsequent lead optimization, and interpret site-directed mutagenesis (SDM) data from a molecular perspective. In this review, we showcase selected modeling-based and guided strategies that were applied to elucidate the binding of agonists to the A₃AR and discuss the challenges associated with an accurate prediction of the receptor extracellular vestibule through homology modeling from the available X-ray templates.
- Subjects :
- Adenosine analogs & derivatives
Adenosine pharmacology
Adenosine A3 Receptor Agonists pharmacology
Adenosine A3 Receptor Antagonists chemical synthesis
Adenosine A3 Receptor Antagonists pharmacology
Anti-Inflammatory Agents pharmacology
Antineoplastic Agents pharmacology
Cardiotonic Agents pharmacology
Drug Design
Humans
Ligands
Molecular Docking Simulation
Molecular Dynamics Simulation
Mutagenesis, Site-Directed
Protein Binding
Protein Conformation
Receptor, Adenosine A3 genetics
Receptor, Adenosine A3 metabolism
Structural Homology, Protein
Structure-Activity Relationship
Adenosine chemical synthesis
Adenosine A3 Receptor Agonists chemical synthesis
Anti-Inflammatory Agents chemical synthesis
Antineoplastic Agents chemical synthesis
Cardiotonic Agents chemical synthesis
Receptor, Adenosine A3 chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1420-3049
- Volume :
- 22
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecules (Basel, Switzerland)
- Publication Type :
- Academic Journal
- Accession number :
- 28287473
- Full Text :
- https://doi.org/10.3390/molecules22030449