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3-Chlorotyramine Acting as Ligand of the D2 Dopamine Receptor. Molecular Modeling, Synthesis and D2 Receptor Affinity.

Authors :
Angelina E
Andujar S
Moreno L
Garibotto F
Párraga J
Peruchena N
Cabedo N
Villecco M
Cortes D
Enriz RD
Source :
Molecular informatics [Mol Inform] 2015 Jan; Vol. 34 (1), pp. 28-43. Date of Electronic Publication: 2014 Nov 27.
Publication Year :
2015

Abstract

We synthesized and tested 3-chlorotyramine as a ligand of the D2 dopamine receptor. This compound displayed a similar affinity by this receptor to that previously reported for dopamine. In order to understand further the experimental results we performed a molecular modeling study of 3-chlorotyramine and structurally related compounds. By combining molecular dynamics simulations with semiempirical (PM6), ab initio and density functional theory calculations, a simple and generally applicable procedure to evaluate the binding energies of these ligands interacting with the D2 dopamine receptors is reported here. These results provided a clear picture of the binding interactions of these compounds from both structural and energetic view points. A reduced model for the binding pocket was used. This approach allowed us to perform more accurate quantum mechanical calculations as well as to obtain a detailed electronic analysis using the Quantum Theory of Atoms in Molecules (QTAIM) technique. Molecular aspects of the binding interactions between ligands and the D2 dopamine receptor are discussed in detail. A good correlation between the relative binding energies obtained from theoretical calculations and experimental IC50 values was obtained. These results allowed us to predict that 3-chlorotyramine possesses a significant affinity by the D2 -DR. Our theoretical predictions were experimentally corroborated when we synthesized and tested 3-chlorotyramine which displayed a similar affinity by the D2 -DR to that reported for DA.<br /> (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Details

Language :
English
ISSN :
1868-1751
Volume :
34
Issue :
1
Database :
MEDLINE
Journal :
Molecular informatics
Publication Type :
Academic Journal
Accession number :
27490860
Full Text :
https://doi.org/10.1002/minf.201400093