Exploration of N-arylpiperazine Binding Sites of D2 Dopaminergic Receptor
Apstrakt
The crystal structures of the D3 dopamine receptor and several other G-protein coupled receptors (GPCRs) were published in recent times. Those 3D structures are used by us and other scientists as a template for the homology modeling and ligand docking analysis of related GPCRs. Our main scientific interest lies in the field of pharmacologically active N-arylpiperazines that exhibit antipsychotic and/or antidepressant properties, and as such are dopaminergic and serotonergic receptor ligands. In this short review article we are presenting synthesis and biological data on the new N-arylpipereazine as well our results on molecular modeling of the interactions of those N-arylpiperazines with the model of D2 dopamine receptors. To obtain that model the crystal structure of the D3 dopamine receptor was used. Our results show that the N-arylpiperazines binding site consists of two pockets: one is the orthosteric binding site where the N-arylpiperazine part of the ligand is docked and the seco...nd is a non-canonical accessory binding site for N-arylpipereazine that is formed by a second extracellular loop (ecl2) of the receptor. Until now, the structure of this receptor region was unresolved in crystal structure analyses of the D3 dopamine receptor. To get a more complete picture of the ligand - receptor interaction, DFT quantum mechanical calculations on N-arylpiperazine were performed and the obtained models were used to examine those interactions.
Ključne reči:
Dopamine D2 receptor / G-protein coupled receptors / molecular modelling / N-arylpiperazinesIzvor:
Mini-Reviews in Medicinal Chemistry, 2015, 15, 12, 988-1001Izdavač:
- Bentham Science Publ Ltd, Sharjah
Finansiranje / projekti:
DOI: 10.2174/138955751512150731112448
ISSN: 1389-5575
PubMed: 25723457
WoS: 000358803500005
Scopus: 2-s2.0-84939832374
Institucija/grupa
IHTMTY - JOUR AU - Šoškić, Vukić AU - Šukalović, Vladimir AU - Kostić Rajačić, Slađana PY - 2015 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/1619 AB - The crystal structures of the D3 dopamine receptor and several other G-protein coupled receptors (GPCRs) were published in recent times. Those 3D structures are used by us and other scientists as a template for the homology modeling and ligand docking analysis of related GPCRs. Our main scientific interest lies in the field of pharmacologically active N-arylpiperazines that exhibit antipsychotic and/or antidepressant properties, and as such are dopaminergic and serotonergic receptor ligands. In this short review article we are presenting synthesis and biological data on the new N-arylpipereazine as well our results on molecular modeling of the interactions of those N-arylpiperazines with the model of D2 dopamine receptors. To obtain that model the crystal structure of the D3 dopamine receptor was used. Our results show that the N-arylpiperazines binding site consists of two pockets: one is the orthosteric binding site where the N-arylpiperazine part of the ligand is docked and the second is a non-canonical accessory binding site for N-arylpipereazine that is formed by a second extracellular loop (ecl2) of the receptor. Until now, the structure of this receptor region was unresolved in crystal structure analyses of the D3 dopamine receptor. To get a more complete picture of the ligand - receptor interaction, DFT quantum mechanical calculations on N-arylpiperazine were performed and the obtained models were used to examine those interactions. PB - Bentham Science Publ Ltd, Sharjah T2 - Mini-Reviews in Medicinal Chemistry T1 - Exploration of N-arylpiperazine Binding Sites of D2 Dopaminergic Receptor VL - 15 IS - 12 SP - 988 EP - 1001 DO - 10.2174/138955751512150731112448 ER -
@article{ author = "Šoškić, Vukić and Šukalović, Vladimir and Kostić Rajačić, Slađana", year = "2015", abstract = "The crystal structures of the D3 dopamine receptor and several other G-protein coupled receptors (GPCRs) were published in recent times. Those 3D structures are used by us and other scientists as a template for the homology modeling and ligand docking analysis of related GPCRs. Our main scientific interest lies in the field of pharmacologically active N-arylpiperazines that exhibit antipsychotic and/or antidepressant properties, and as such are dopaminergic and serotonergic receptor ligands. In this short review article we are presenting synthesis and biological data on the new N-arylpipereazine as well our results on molecular modeling of the interactions of those N-arylpiperazines with the model of D2 dopamine receptors. To obtain that model the crystal structure of the D3 dopamine receptor was used. Our results show that the N-arylpiperazines binding site consists of two pockets: one is the orthosteric binding site where the N-arylpiperazine part of the ligand is docked and the second is a non-canonical accessory binding site for N-arylpipereazine that is formed by a second extracellular loop (ecl2) of the receptor. Until now, the structure of this receptor region was unresolved in crystal structure analyses of the D3 dopamine receptor. To get a more complete picture of the ligand - receptor interaction, DFT quantum mechanical calculations on N-arylpiperazine were performed and the obtained models were used to examine those interactions.", publisher = "Bentham Science Publ Ltd, Sharjah", journal = "Mini-Reviews in Medicinal Chemistry", title = "Exploration of N-arylpiperazine Binding Sites of D2 Dopaminergic Receptor", volume = "15", number = "12", pages = "988-1001", doi = "10.2174/138955751512150731112448" }
Šoškić, V., Šukalović, V.,& Kostić Rajačić, S.. (2015). Exploration of N-arylpiperazine Binding Sites of D2 Dopaminergic Receptor. in Mini-Reviews in Medicinal Chemistry Bentham Science Publ Ltd, Sharjah., 15(12), 988-1001. https://doi.org/10.2174/138955751512150731112448
Šoškić V, Šukalović V, Kostić Rajačić S. Exploration of N-arylpiperazine Binding Sites of D2 Dopaminergic Receptor. in Mini-Reviews in Medicinal Chemistry. 2015;15(12):988-1001. doi:10.2174/138955751512150731112448 .
Šoškić, Vukić, Šukalović, Vladimir, Kostić Rajačić, Slađana, "Exploration of N-arylpiperazine Binding Sites of D2 Dopaminergic Receptor" in Mini-Reviews in Medicinal Chemistry, 15, no. 12 (2015):988-1001, https://doi.org/10.2174/138955751512150731112448 . .