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Simulation and comparative analysis of binding modes of nucleoside and non-nucleoside agonists at the A(2B) adenosine receptor

PURPOSE: A(2B) receptor agonists are studied as possible therapeutic tools for a variety of pathological conditions. Unfortunately, medicinal chemistry efforts have led to the development of a limited number of potent agonists of this receptor, in most cases with a low or no selectivity versus the o...

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Autores principales: Dal Ben, Diego, Buccioni, Michela, Lambertucci, Catia, Thomas, Ajiroghene, Volpini, Rosaria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215817/
https://www.ncbi.nlm.nih.gov/pubmed/25505666
http://dx.doi.org/10.1186/2193-9616-1-24
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author Dal Ben, Diego
Buccioni, Michela
Lambertucci, Catia
Thomas, Ajiroghene
Volpini, Rosaria
author_facet Dal Ben, Diego
Buccioni, Michela
Lambertucci, Catia
Thomas, Ajiroghene
Volpini, Rosaria
author_sort Dal Ben, Diego
collection PubMed
description PURPOSE: A(2B) receptor agonists are studied as possible therapeutic tools for a variety of pathological conditions. Unfortunately, medicinal chemistry efforts have led to the development of a limited number of potent agonists of this receptor, in most cases with a low or no selectivity versus the other adenosine receptor subtypes. Among the developed molecules, two structural families of compounds have been identified based on nucleoside and non-nucleoside (pyridine) scaffolds. The aim of this work is to analyse the binding mode of these molecules at 3D models of the human A(2B) receptor to identify possible common interaction features and the key receptor residues involved in ligand interaction. METHODS: The A(2B) receptor models are built by using two recently published crystal structures of the human A(2A) receptor in complex with two different agonists. The developed models are used as targets for molecular docking studies of nucleoside and non-nucleoside agonists. The generated docking conformations are subjected to energy minimization and rescoring by using three different scoring functions. Further analysis of top-score conformations are performed with a tool evaluating the interaction energy between the ligand and the binding site residues. RESULTS: Results suggest a set of common interaction points between the two structural families of agonists and the receptor binding site, as evidenced by the superimposition of docking conformations and by analysis of interaction energy with the receptor residues. CONCLUSIONS: The obtained results show that there is a conserved pattern of interaction between the A(2B) receptor and its agonists. These information and can provide useful data to support the design and the development of A(2B) receptor agonists belonging to nucleoside or non-nucleoside structural families. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-9616-1-24) contains supplementary material, which is available to authorized users.
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spelling pubmed-42158172014-12-11 Simulation and comparative analysis of binding modes of nucleoside and non-nucleoside agonists at the A(2B) adenosine receptor Dal Ben, Diego Buccioni, Michela Lambertucci, Catia Thomas, Ajiroghene Volpini, Rosaria In Silico Pharmacol Original Research PURPOSE: A(2B) receptor agonists are studied as possible therapeutic tools for a variety of pathological conditions. Unfortunately, medicinal chemistry efforts have led to the development of a limited number of potent agonists of this receptor, in most cases with a low or no selectivity versus the other adenosine receptor subtypes. Among the developed molecules, two structural families of compounds have been identified based on nucleoside and non-nucleoside (pyridine) scaffolds. The aim of this work is to analyse the binding mode of these molecules at 3D models of the human A(2B) receptor to identify possible common interaction features and the key receptor residues involved in ligand interaction. METHODS: The A(2B) receptor models are built by using two recently published crystal structures of the human A(2A) receptor in complex with two different agonists. The developed models are used as targets for molecular docking studies of nucleoside and non-nucleoside agonists. The generated docking conformations are subjected to energy minimization and rescoring by using three different scoring functions. Further analysis of top-score conformations are performed with a tool evaluating the interaction energy between the ligand and the binding site residues. RESULTS: Results suggest a set of common interaction points between the two structural families of agonists and the receptor binding site, as evidenced by the superimposition of docking conformations and by analysis of interaction energy with the receptor residues. CONCLUSIONS: The obtained results show that there is a conserved pattern of interaction between the A(2B) receptor and its agonists. These information and can provide useful data to support the design and the development of A(2B) receptor agonists belonging to nucleoside or non-nucleoside structural families. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-9616-1-24) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2013-12-20 /pmc/articles/PMC4215817/ /pubmed/25505666 http://dx.doi.org/10.1186/2193-9616-1-24 Text en © Dal Ben et al.; licensee Springer. 2013 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Dal Ben, Diego
Buccioni, Michela
Lambertucci, Catia
Thomas, Ajiroghene
Volpini, Rosaria
Simulation and comparative analysis of binding modes of nucleoside and non-nucleoside agonists at the A(2B) adenosine receptor
title Simulation and comparative analysis of binding modes of nucleoside and non-nucleoside agonists at the A(2B) adenosine receptor
title_full Simulation and comparative analysis of binding modes of nucleoside and non-nucleoside agonists at the A(2B) adenosine receptor
title_fullStr Simulation and comparative analysis of binding modes of nucleoside and non-nucleoside agonists at the A(2B) adenosine receptor
title_full_unstemmed Simulation and comparative analysis of binding modes of nucleoside and non-nucleoside agonists at the A(2B) adenosine receptor
title_short Simulation and comparative analysis of binding modes of nucleoside and non-nucleoside agonists at the A(2B) adenosine receptor
title_sort simulation and comparative analysis of binding modes of nucleoside and non-nucleoside agonists at the a(2b) adenosine receptor
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215817/
https://www.ncbi.nlm.nih.gov/pubmed/25505666
http://dx.doi.org/10.1186/2193-9616-1-24
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