TY  - JOUR
AU  - Šukalović, Vladimir
AU  - Šoškić, Vukić
AU  - Ignjatović, Đurđica
AU  - Andrić, Deana
AU  - Penjišević, Jelena
AU  - Kostić-Rajačić, Slađana
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2255
AB  - The dopaminergic receptor system has been the focus for the development
   of new pharmacotherapeutic agents targeting a number of central nervous
   system related disorders, such as drug addiction, schizophrenia,
   depression, and Parkinson's disease, to name just a few. To date, the
   crystal structure for the human D2 receptor is not known, despite its
   vital function and importance as a therapeutic target. Herein, a recent
   advancement in the determination of key receptor ligand interactions for
   the available arylpiperazine-like ligands, using a D2 receptor model
   based on the crystal structure of the D3 receptor is presented. To
   determine key interactions responsible for high dopaminergic activity,
   computer-docking analysis was used together with experimental data. A
   total of 4 dopaminergic ligands showing moderate to high affinity were
   tested and the obtained results rationalized using ligand structures
   docked into the proposed D2 receptor model.
T2  - Journal of the Serbian Chemical Society
T1  - Investigation of key interactions between the second extracellular loop of dopamine D2 receptor and several hydroxy-N-{[2-(4-phenyl-piperaziny-1-yl)ethyl]phenyl}-nicotinamides
IS  - 12
VL  - 79
DO  - 10.2298/JSC140423070S
SP  - 1461
EP  - 1467
ER  - 

@article{
author = "Šukalović, Vladimir and Šoškić, Vukić and Ignjatović, Đurđica and Andrić, Deana and Penjišević, Jelena and Kostić-Rajačić, Slađana",
year = "2014",
abstract = "The dopaminergic receptor system has been the focus for the development
   of new pharmacotherapeutic agents targeting a number of central nervous
   system related disorders, such as drug addiction, schizophrenia,
   depression, and Parkinson's disease, to name just a few. To date, the
   crystal structure for the human D2 receptor is not known, despite its
   vital function and importance as a therapeutic target. Herein, a recent
   advancement in the determination of key receptor ligand interactions for
   the available arylpiperazine-like ligands, using a D2 receptor model
   based on the crystal structure of the D3 receptor is presented. To
   determine key interactions responsible for high dopaminergic activity,
   computer-docking analysis was used together with experimental data. A
   total of 4 dopaminergic ligands showing moderate to high affinity were
   tested and the obtained results rationalized using ligand structures
   docked into the proposed D2 receptor model.",
journal = "Journal of the Serbian Chemical Society",
title = "Investigation of key interactions between the second extracellular loop of dopamine D2 receptor and several hydroxy-N-{[2-(4-phenyl-piperaziny-1-yl)ethyl]phenyl}-nicotinamides",
number = "12",
volume = "79",
doi = "10.2298/JSC140423070S",
pages = "1461-1467"
}

Šukalović, V., Šoškić, V., Ignjatović, Đ., Andrić, D., Penjišević, J.,& Kostić-Rajačić, S.. (2014). Investigation of key interactions between the second extracellular loop of dopamine D2 receptor and several hydroxy-N-{[2-(4-phenyl-piperaziny-1-yl)ethyl]phenyl}-nicotinamides. in Journal of the Serbian Chemical Society, 79(12), 1461-1467.
https://doi.org/10.2298/JSC140423070S

Šukalović V, Šoškić V, Ignjatović Đ, Andrić D, Penjišević J, Kostić-Rajačić S. Investigation of key interactions between the second extracellular loop of dopamine D2 receptor and several hydroxy-N-{[2-(4-phenyl-piperaziny-1-yl)ethyl]phenyl}-nicotinamides. in Journal of the Serbian Chemical Society. 2014;79(12):1461-1467.
doi:10.2298/JSC140423070S .

Šukalović, Vladimir, Šoškić, Vukić, Ignjatović, Đurđica, Andrić, Deana, Penjišević, Jelena, Kostić-Rajačić, Slađana, "Investigation of key interactions between the second extracellular loop of dopamine D2 receptor and several hydroxy-N-{[2-(4-phenyl-piperaziny-1-yl)ethyl]phenyl}-nicotinamides" in Journal of the Serbian Chemical Society, 79, no. 12 (2014):1461-1467,
https://doi.org/10.2298/JSC140423070S . .

TY  - JOUR
AU  - Šukalović, Vladimir
AU  - Bogdan, Anca Elena
AU  - Tovilović-Kovačević, Gordana
AU  - Ignjatović, Đurđica
AU  - Andrić, Deana
AU  - Kostić-Rajačić, Slađana
AU  - Šoškić, Vukić
PY  - 2013
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6804
AB  - The ratio of affinities toward the dopamine D-2 and the 5-hydroxytryptamine 5-HT1A receptors is one of the important parameters that determine the efficiency of antipsychotic drugs. Here, we present the synthesis of ortho-, meta-, and para-N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides and their structure-activity relationship studies on dopamine D-2 and 5-hydroxytryptamine 5-HT1A receptors. It was shown that the biological activity of the described ligands strongly depends on their topology as well as on the nature of the heteroaryl group in the head of the molecules. Docking simulations together with conformational analysis revealed a rational explanation for the ligands' behavior. The molecular model of receptor-ligand interactions described herein provided us with a tool for the rational design of new compounds with a favorable D-2/5-HT1A profile.
PB  - Weinheim: Wiley-V C H Verlag Gmbh
T2  - Archiv der Pharmazie
T1  - N-{[2-(4-Phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides with Dopamine D-2 and 5-Hydroxytryptamine 5HT(1A) Activity: Synthesis, Testing, and Molecular Modeling
IS  - 10
VL  - 346
DO  - 10.1002/ardp.201300189
SP  - 708
EP  - 717
ER  - 

@article{
author = "Šukalović, Vladimir and Bogdan, Anca Elena and Tovilović-Kovačević, Gordana and Ignjatović, Đurđica and Andrić, Deana and Kostić-Rajačić, Slađana and Šoškić, Vukić",
year = "2013",
abstract = "The ratio of affinities toward the dopamine D-2 and the 5-hydroxytryptamine 5-HT1A receptors is one of the important parameters that determine the efficiency of antipsychotic drugs. Here, we present the synthesis of ortho-, meta-, and para-N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides and their structure-activity relationship studies on dopamine D-2 and 5-hydroxytryptamine 5-HT1A receptors. It was shown that the biological activity of the described ligands strongly depends on their topology as well as on the nature of the heteroaryl group in the head of the molecules. Docking simulations together with conformational analysis revealed a rational explanation for the ligands' behavior. The molecular model of receptor-ligand interactions described herein provided us with a tool for the rational design of new compounds with a favorable D-2/5-HT1A profile.",
publisher = "Weinheim: Wiley-V C H Verlag Gmbh",
journal = "Archiv der Pharmazie",
title = "N-{[2-(4-Phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides with Dopamine D-2 and 5-Hydroxytryptamine 5HT(1A) Activity: Synthesis, Testing, and Molecular Modeling",
number = "10",
volume = "346",
doi = "10.1002/ardp.201300189",
pages = "708-717"
}

Šukalović, V., Bogdan, A. E., Tovilović-Kovačević, G., Ignjatović, Đ., Andrić, D., Kostić-Rajačić, S.,& Šoškić, V.. (2013). N-{[2-(4-Phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides with Dopamine D-2 and 5-Hydroxytryptamine 5HT(1A) Activity: Synthesis, Testing, and Molecular Modeling. in Archiv der Pharmazie
Weinheim: Wiley-V C H Verlag Gmbh., 346(10), 708-717.
https://doi.org/10.1002/ardp.201300189

Šukalović V, Bogdan AE, Tovilović-Kovačević G, Ignjatović Đ, Andrić D, Kostić-Rajačić S, Šoškić V. N-{[2-(4-Phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides with Dopamine D-2 and 5-Hydroxytryptamine 5HT(1A) Activity: Synthesis, Testing, and Molecular Modeling. in Archiv der Pharmazie. 2013;346(10):708-717.
doi:10.1002/ardp.201300189 .

Šukalović, Vladimir, Bogdan, Anca Elena, Tovilović-Kovačević, Gordana, Ignjatović, Đurđica, Andrić, Deana, Kostić-Rajačić, Slađana, Šoškić, Vukić, "N-{[2-(4-Phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides with Dopamine D-2 and 5-Hydroxytryptamine 5HT(1A) Activity: Synthesis, Testing, and Molecular Modeling" in Archiv der Pharmazie, 346, no. 10 (2013):708-717,
https://doi.org/10.1002/ardp.201300189 . .

TY  - JOUR
AU  - Ignjatović, Đurđica
AU  - Šukalović, Vladimir B.
AU  - Tasić, Bosiljka
AU  - Kostić-Rajačić, Slađana V.
AU  - Šoškić, Vukić
PY  - 2002
PY  - 2002
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/18
AB  - In order to find the essential structural motif of the D2L dopamine receptor necessary for the interaction with a-subunit of Gi1 protein, four fragments of the third cytoplasmic loop (CPL3) of this receptor were cloned, expressed in E. coli and purified. After that, fusion proteins with glutathione-S-transferase (GST) were prepared and the interactions quantified by a colorimetric assay for GST activity determination. The presence of D2L-CPL3 fragment-Gia1 complexes was detected by SDS-polyacrylamide gel electrophoresis (PAGE). Kd values for the interaction of the three fragments with Gia1 were similar and in nmol/L range of concentrations, while the peptide representing the insert in the long form of the dopamine D2 receptor expressed about 10-fold lower binding affinity. These results could serve to design new therapeutic agents that might act at the level of receptor/G protein interaction rather than at the level of ligand-receptor binding.
AB  - U cilju pronalaženja bitnih strukturnih motiva potrebnih za interakciju sa a podjedinicom Gi1 proteina klonirana su, eksprimirana i prečišćena 4 fragmenta treće citoplazmatične petlje (CPL3) dopaminskog D2L receptora koji su dalje pripremljeni kao fuzioni proteini sa glutation-S-transferazom (GST). Interakcije su kvantifikovane bojenom reakcijom za određivanje aktivnosti GST. Postojanje kompleksa D2L-CPL3 fragment- Gia1 je dokazano elektroforetskom analizom na SDS-poliakrilamidnom gelu (PAGE). Kd vrednosti za tri fragmenta su bile vrlo slične i u nmol/L opsegu koncentracija, dok je peptid koji predstavlja insert u dugom obliku dopaminskog D2 receptora posedovao oko 10 puta manji afinitet vezivanja za Gia1. Ovi rezultati mogu biti osnova za sintezu novih terapeutskih agenasa koji bi delovali na nivou interakcije receptora i G proteina umesto na nivou vezivanja liganda za receptor.
PB  - Društvo medicinskih biohemičara Srbije i Crne Gore
T2  - Yugoslav Medical Biochemistry
T1  - Interakcija različitih fragmenata treće citoplazmatične petlje dopaminskog d2l receptora čoveka sa a-podjedinicom gi1 proteina - moguća terapeutska primena
T1  - Interaction of different third intracellular loop fragments of human dopamine d2l receptor with a-subunit of gi1 protein - prospective therapeutic application
IS  - 1
VL  - 21
DO  - 10.2298/JMH0201009I
SP  - 9
EP  - 14
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_18
ER  - 

@article{
author = "Ignjatović, Đurđica and Šukalović, Vladimir B. and Tasić, Bosiljka and Kostić-Rajačić, Slađana V. and Šoškić, Vukić",
year = "2002, 2002",
abstract = "In order to find the essential structural motif of the D2L dopamine receptor necessary for the interaction with a-subunit of Gi1 protein, four fragments of the third cytoplasmic loop (CPL3) of this receptor were cloned, expressed in E. coli and purified. After that, fusion proteins with glutathione-S-transferase (GST) were prepared and the interactions quantified by a colorimetric assay for GST activity determination. The presence of D2L-CPL3 fragment-Gia1 complexes was detected by SDS-polyacrylamide gel electrophoresis (PAGE). Kd values for the interaction of the three fragments with Gia1 were similar and in nmol/L range of concentrations, while the peptide representing the insert in the long form of the dopamine D2 receptor expressed about 10-fold lower binding affinity. These results could serve to design new therapeutic agents that might act at the level of receptor/G protein interaction rather than at the level of ligand-receptor binding., U cilju pronalaženja bitnih strukturnih motiva potrebnih za interakciju sa a podjedinicom Gi1 proteina klonirana su, eksprimirana i prečišćena 4 fragmenta treće citoplazmatične petlje (CPL3) dopaminskog D2L receptora koji su dalje pripremljeni kao fuzioni proteini sa glutation-S-transferazom (GST). Interakcije su kvantifikovane bojenom reakcijom za određivanje aktivnosti GST. Postojanje kompleksa D2L-CPL3 fragment- Gia1 je dokazano elektroforetskom analizom na SDS-poliakrilamidnom gelu (PAGE). Kd vrednosti za tri fragmenta su bile vrlo slične i u nmol/L opsegu koncentracija, dok je peptid koji predstavlja insert u dugom obliku dopaminskog D2 receptora posedovao oko 10 puta manji afinitet vezivanja za Gia1. Ovi rezultati mogu biti osnova za sintezu novih terapeutskih agenasa koji bi delovali na nivou interakcije receptora i G proteina umesto na nivou vezivanja liganda za receptor.",
publisher = "Društvo medicinskih biohemičara Srbije i Crne Gore",
journal = "Yugoslav Medical Biochemistry",
title = "Interakcija različitih fragmenata treće citoplazmatične petlje dopaminskog d2l receptora čoveka sa a-podjedinicom gi1 proteina - moguća terapeutska primena, Interaction of different third intracellular loop fragments of human dopamine d2l receptor with a-subunit of gi1 protein - prospective therapeutic application",
number = "1",
volume = "21",
doi = "10.2298/JMH0201009I",
pages = "9-14",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_18"
}

Ignjatović, Đ., Šukalović, V. B., Tasić, B., Kostić-Rajačić, S. V.,& Šoškić, V.. (2002). Interakcija različitih fragmenata treće citoplazmatične petlje dopaminskog d2l receptora čoveka sa a-podjedinicom gi1 proteina - moguća terapeutska primena. in Yugoslav Medical Biochemistry
Društvo medicinskih biohemičara Srbije i Crne Gore., 21(1), 9-14.
https://doi.org/10.2298/JMH0201009I
https://hdl.handle.net/21.15107/rcub_ibiss_18

Ignjatović Đ, Šukalović VB, Tasić B, Kostić-Rajačić SV, Šoškić V. Interakcija različitih fragmenata treće citoplazmatične petlje dopaminskog d2l receptora čoveka sa a-podjedinicom gi1 proteina - moguća terapeutska primena. in Yugoslav Medical Biochemistry. 2002;21(1):9-14.
doi:10.2298/JMH0201009I
https://hdl.handle.net/21.15107/rcub_ibiss_18 .

Ignjatović, Đurđica, Šukalović, Vladimir B., Tasić, Bosiljka, Kostić-Rajačić, Slađana V., Šoškić, Vukić, "Interakcija različitih fragmenata treće citoplazmatične petlje dopaminskog d2l receptora čoveka sa a-podjedinicom gi1 proteina - moguća terapeutska primena" in Yugoslav Medical Biochemistry, 21, no. 1 (2002):9-14,
https://doi.org/10.2298/JMH0201009I .,
https://hdl.handle.net/21.15107/rcub_ibiss_18 .