TY  - JOUR
AU  - Radisavljević, Snežana
AU  - Bratsos, Ioannis
AU  - Scheurer, Andreas
AU  - Korzekwa, Jana
AU  - Masnikosa, Romana
AU  - Tot, Aleksandar
AU  - Gligorijević, Nevenka N.
AU  - Radulović, Siniša S.
AU  - Rilak Simović, Ana
PY  - 2018
UR  - http://xlink.rsc.org/?DOI=C8DT02903B
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7894
AB  - With the aim of assessing whether Au(iii) compounds with pincer type ligands might be utilized as potential antitumor agents, three new monofunctional Au(iii) complexes of the general formula [Au(N-N'-N)Cl]Cl-2, where N-N'-N = 2,6-bis(5-tert-butyl-1H-pyrazol-3-yl)pyridine (H2LtBu, 1), 2,6-bis(5-tert-butyl-1-methyl-1H-pyrazol-3-yl)pyridine (Me2LtBu, 2) or 2,6-bis((4S,7R)-1,7,8,8-tetramethyl-4,5,6,7-tetrahydro-1H-4,7-methanoindazol-3-yl)pyridine (Me-2*L, 3) were synthesized. All complexes were characterized by elemental analysis, spectroscopic techniques (IR, UV-Vis, 1D and 2D NMR) and mass spectrometry (MALDI TOF MS). The chemical behavior of the complexes under physiological conditions was studied by UV-Vis spectroscopy, which showed that all compounds were remarkably stable and that the gold center remained in the 3+ oxidation state. The kinetics and the mechanism of the reaction of complexes 1-3 with guanine derivatives (i.e. guanosine (Guo) and guanosine-5-monophosphate (5-GMP)) and calf thymus DNA (CT DNA) were studied by stopped-flow spectroscopy. The three complexes displayed moderately different rate constants in their reactions with Guo, 5-GMP and CT DNA, which can be explained by the steric hindrance and sigma-donicity of the methyl substituent on the bis-pyrazolylpyridine fragment in complexes 2 and 3. The measured enthalpies and entropies of activation (Delta H-not equal > 0, Delta S-not equal < 0) supported an associative mechanism for the substitution process. The interaction of the newly synthesized complexes 1-3 with CT DNA was investigated by UV-Vis and fluorescence spectroscopy, and also by viscosity measurements, which all indicated that complexes 1-3 bound to CT DNA with moderate binding affinity (K-b = 1.6-5.7 x 10(3) M-1) and stabilized the duplex of CT DNA. Molecular docking indicated that complexes 1-3 interacted with DNA via intercalation. Complex 1 reduced the cell survival of all the investigated cell lines (A549, A375, and LS-174) with IC50 values being up to 20 mu M. We have shown that 1 induced perturbations of the cell cycle and led to apoptosis in human melanoma A375 cells. Complex 1 also affected the level of reactive oxygen species (ROS) in the same cells. However, pre-treatment of A375 cells with NAC (ROS scavenger) reversed the effect of 1 on their survival.
T2  - Dalton Transactions
T1  - New gold pincer-type complexes: synthesis, characterization, DNA binding studies and cytotoxicity
VL  - 47
IS  - 38
SP  - 13696
EP  - 13712
DO  - 10.1039/C8DT02903B
ER  - 

@article{
author = "Radisavljević, Snežana and Bratsos, Ioannis and Scheurer, Andreas and Korzekwa, Jana and Masnikosa, Romana and Tot, Aleksandar and Gligorijević, Nevenka N. and Radulović, Siniša S. and Rilak Simović, Ana",
year = "2018",
abstract = "With the aim of assessing whether Au(iii) compounds with pincer type ligands might be utilized as potential antitumor agents, three new monofunctional Au(iii) complexes of the general formula [Au(N-N'-N)Cl]Cl-2, where N-N'-N = 2,6-bis(5-tert-butyl-1H-pyrazol-3-yl)pyridine (H2LtBu, 1), 2,6-bis(5-tert-butyl-1-methyl-1H-pyrazol-3-yl)pyridine (Me2LtBu, 2) or 2,6-bis((4S,7R)-1,7,8,8-tetramethyl-4,5,6,7-tetrahydro-1H-4,7-methanoindazol-3-yl)pyridine (Me-2*L, 3) were synthesized. All complexes were characterized by elemental analysis, spectroscopic techniques (IR, UV-Vis, 1D and 2D NMR) and mass spectrometry (MALDI TOF MS). The chemical behavior of the complexes under physiological conditions was studied by UV-Vis spectroscopy, which showed that all compounds were remarkably stable and that the gold center remained in the 3+ oxidation state. The kinetics and the mechanism of the reaction of complexes 1-3 with guanine derivatives (i.e. guanosine (Guo) and guanosine-5-monophosphate (5-GMP)) and calf thymus DNA (CT DNA) were studied by stopped-flow spectroscopy. The three complexes displayed moderately different rate constants in their reactions with Guo, 5-GMP and CT DNA, which can be explained by the steric hindrance and sigma-donicity of the methyl substituent on the bis-pyrazolylpyridine fragment in complexes 2 and 3. The measured enthalpies and entropies of activation (Delta H-not equal > 0, Delta S-not equal < 0) supported an associative mechanism for the substitution process. The interaction of the newly synthesized complexes 1-3 with CT DNA was investigated by UV-Vis and fluorescence spectroscopy, and also by viscosity measurements, which all indicated that complexes 1-3 bound to CT DNA with moderate binding affinity (K-b = 1.6-5.7 x 10(3) M-1) and stabilized the duplex of CT DNA. Molecular docking indicated that complexes 1-3 interacted with DNA via intercalation. Complex 1 reduced the cell survival of all the investigated cell lines (A549, A375, and LS-174) with IC50 values being up to 20 mu M. We have shown that 1 induced perturbations of the cell cycle and led to apoptosis in human melanoma A375 cells. Complex 1 also affected the level of reactive oxygen species (ROS) in the same cells. However, pre-treatment of A375 cells with NAC (ROS scavenger) reversed the effect of 1 on their survival.",
journal = "Dalton Transactions",
title = "New gold pincer-type complexes: synthesis, characterization, DNA binding studies and cytotoxicity",
volume = "47",
number = "38",
pages = "13696-13712",
doi = "10.1039/C8DT02903B"
}

Radisavljević, S., Bratsos, I., Scheurer, A., Korzekwa, J., Masnikosa, R., Tot, A., Gligorijević, N. N., Radulović, S. S.,& Rilak Simović, A.. (2018). New gold pincer-type complexes: synthesis, characterization, DNA binding studies and cytotoxicity. in Dalton Transactions, 47(38), 13696-13712.
https://doi.org/10.1039/C8DT02903B

Radisavljević S, Bratsos I, Scheurer A, Korzekwa J, Masnikosa R, Tot A, Gligorijević NN, Radulović SS, Rilak Simović A. New gold pincer-type complexes: synthesis, characterization, DNA binding studies and cytotoxicity. in Dalton Transactions. 2018;47(38):13696-13712.
doi:10.1039/C8DT02903B .

Radisavljević, Snežana, Bratsos, Ioannis, Scheurer, Andreas, Korzekwa, Jana, Masnikosa, Romana, Tot, Aleksandar, Gligorijević, Nevenka N., Radulović, Siniša S., Rilak Simović, Ana, "New gold pincer-type complexes: synthesis, characterization, DNA binding studies and cytotoxicity" in Dalton Transactions, 47, no. 38 (2018):13696-13712,
https://doi.org/10.1039/C8DT02903B . .

TY  - JOUR
AU  - Baroud, Afya A.
AU  - Mihajlović-Lalić, Ljiljana E.
AU  - Gligorijević, Nevenka N.
AU  - Aranđelović, Sandra
AU  - Stanković, Dalibor M.
AU  - Radulović, Siniša S.
AU  - Van Hecke, Kristof
AU  - Savić, Aleksandar
AU  - Grgurić-Šipka, Sanja
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1438
AB  - Complexes 1-4, [Ru(L)(bpy)(2)]PF6, where bpy=2,2-bipyridine; HL=3-methylpyridine-2-carboxylic acid (HL1), 6-methylpyridine-2-carboxylic acid (HL2), 5-bromopyridine-2-carboxylic acid (HL3) and 6-bromopyridine-2-carboxylic acid (HL4), were synthesized and characterized. The electrochemical character of the complexes was investigated by cyclic voltammetry revealing two reversible reduction waves in the negative range of potentials, most likely due to a reduction of the bipyridine moiety. Cytotoxicity studies by MTT assay for 72h of drug action revealed that 2-4 exhibited moderate activity in cervical human tumor cells (HeLa). Complex 2 exhibited low activity in colon cancer LS-174 cells (180 +/- 10), while all complexes were devoid of activity in lung cancer A549 and non-tumor MRC-5 cells, up to 200M. Combinational studies of the most active complex 2, with pharmacological modulators of cell redox status, L-buthionine-sulfoximine (L-BSO) or N-acetyl-L-cysteine (NAC), showed that when L-BSO potentiated, 2 induced a sub-G1 peak of the cell cycle in the HeLa cell line. UV-vis and cyclic voltammetry were performed in order to investigate the binding mode of 2 to DNA and suggested intercalation for the complex-DNA interaction. [GRAPHICS]
T2  - Journal of Coordination Chemistry
T1  - Ruthenium(II) bipyridine complexes: from synthesis and crystal structures to electrochemical and cytotoxicity investigation
VL  - 70
IS  - 5
SP  - 831
EP  - 847
DO  - 10.1080/00958972.2017.1282611
ER  - 

@article{
author = "Baroud, Afya A. and Mihajlović-Lalić, Ljiljana E. and Gligorijević, Nevenka N. and Aranđelović, Sandra and Stanković, Dalibor M. and Radulović, Siniša S. and Van Hecke, Kristof and Savić, Aleksandar and Grgurić-Šipka, Sanja",
year = "2017",
abstract = "Complexes 1-4, [Ru(L)(bpy)(2)]PF6, where bpy=2,2-bipyridine; HL=3-methylpyridine-2-carboxylic acid (HL1), 6-methylpyridine-2-carboxylic acid (HL2), 5-bromopyridine-2-carboxylic acid (HL3) and 6-bromopyridine-2-carboxylic acid (HL4), were synthesized and characterized. The electrochemical character of the complexes was investigated by cyclic voltammetry revealing two reversible reduction waves in the negative range of potentials, most likely due to a reduction of the bipyridine moiety. Cytotoxicity studies by MTT assay for 72h of drug action revealed that 2-4 exhibited moderate activity in cervical human tumor cells (HeLa). Complex 2 exhibited low activity in colon cancer LS-174 cells (180 +/- 10), while all complexes were devoid of activity in lung cancer A549 and non-tumor MRC-5 cells, up to 200M. Combinational studies of the most active complex 2, with pharmacological modulators of cell redox status, L-buthionine-sulfoximine (L-BSO) or N-acetyl-L-cysteine (NAC), showed that when L-BSO potentiated, 2 induced a sub-G1 peak of the cell cycle in the HeLa cell line. UV-vis and cyclic voltammetry were performed in order to investigate the binding mode of 2 to DNA and suggested intercalation for the complex-DNA interaction. [GRAPHICS]",
journal = "Journal of Coordination Chemistry",
title = "Ruthenium(II) bipyridine complexes: from synthesis and crystal structures to electrochemical and cytotoxicity investigation",
volume = "70",
number = "5",
pages = "831-847",
doi = "10.1080/00958972.2017.1282611"
}

Baroud, A. A., Mihajlović-Lalić, L. E., Gligorijević, N. N., Aranđelović, S., Stanković, D. M., Radulović, S. S., Van Hecke, K., Savić, A.,& Grgurić-Šipka, S.. (2017). Ruthenium(II) bipyridine complexes: from synthesis and crystal structures to electrochemical and cytotoxicity investigation. in Journal of Coordination Chemistry, 70(5), 831-847.
https://doi.org/10.1080/00958972.2017.1282611

Baroud AA, Mihajlović-Lalić LE, Gligorijević NN, Aranđelović S, Stanković DM, Radulović SS, Van Hecke K, Savić A, Grgurić-Šipka S. Ruthenium(II) bipyridine complexes: from synthesis and crystal structures to electrochemical and cytotoxicity investigation. in Journal of Coordination Chemistry. 2017;70(5):831-847.
doi:10.1080/00958972.2017.1282611 .

Baroud, Afya A., Mihajlović-Lalić, Ljiljana E., Gligorijević, Nevenka N., Aranđelović, Sandra, Stanković, Dalibor M., Radulović, Siniša S., Van Hecke, Kristof, Savić, Aleksandar, Grgurić-Šipka, Sanja, "Ruthenium(II) bipyridine complexes: from synthesis and crystal structures to electrochemical and cytotoxicity investigation" in Journal of Coordination Chemistry, 70, no. 5 (2017):831-847,
https://doi.org/10.1080/00958972.2017.1282611 . .

TY  - JOUR
AU  - Baroud, Afya A.
AU  - Mihajlović-Lalić, Ljiljana E.
AU  - Gligorijević, Nevenka N.
AU  - Aranđelović, Sandra
AU  - Stanković, Dalibor M.
AU  - Radulović, Siniša S.
AU  - Van Hecke, Kristof
AU  - Savić, Aleksandar
AU  - Grgurić-Šipka, Sanja
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8852
AB  - Complexes 1-4, [Ru(L)(bpy)(2)]PF6, where bpy=2,2-bipyridine; HL=3-methylpyridine-2-carboxylic acid (HL1), 6-methylpyridine-2-carboxylic acid (HL2), 5-bromopyridine-2-carboxylic acid (HL3) and 6-bromopyridine-2-carboxylic acid (HL4), were synthesized and characterized. The electrochemical character of the complexes was investigated by cyclic voltammetry revealing two reversible reduction waves in the negative range of potentials, most likely due to a reduction of the bipyridine moiety. Cytotoxicity studies by MTT assay for 72h of drug action revealed that 2-4 exhibited moderate activity in cervical human tumor cells (HeLa). Complex 2 exhibited low activity in colon cancer LS-174 cells (180 +/- 10), while all complexes were devoid of activity in lung cancer A549 and non-tumor MRC-5 cells, up to 200M. Combinational studies of the most active complex 2, with pharmacological modulators of cell redox status, L-buthionine-sulfoximine (L-BSO) or N-acetyl-L-cysteine (NAC), showed that when L-BSO potentiated, 2 induced a sub-G1 peak of the cell cycle in the HeLa cell line. UV-vis and cyclic voltammetry were performed in order to investigate the binding mode of 2 to DNA and suggested intercalation for the complex-DNA interaction. [GRAPHICS]
T2  - Journal of Coordination Chemistry
T1  - Ruthenium(II) bipyridine complexes: from synthesis and crystal structures to electrochemical and cytotoxicity investigation
VL  - 70
IS  - 5
SP  - 831
EP  - 847
DO  - 10.1080/00958972.2017.1282611
ER  - 

@article{
author = "Baroud, Afya A. and Mihajlović-Lalić, Ljiljana E. and Gligorijević, Nevenka N. and Aranđelović, Sandra and Stanković, Dalibor M. and Radulović, Siniša S. and Van Hecke, Kristof and Savić, Aleksandar and Grgurić-Šipka, Sanja",
year = "2017",
abstract = "Complexes 1-4, [Ru(L)(bpy)(2)]PF6, where bpy=2,2-bipyridine; HL=3-methylpyridine-2-carboxylic acid (HL1), 6-methylpyridine-2-carboxylic acid (HL2), 5-bromopyridine-2-carboxylic acid (HL3) and 6-bromopyridine-2-carboxylic acid (HL4), were synthesized and characterized. The electrochemical character of the complexes was investigated by cyclic voltammetry revealing two reversible reduction waves in the negative range of potentials, most likely due to a reduction of the bipyridine moiety. Cytotoxicity studies by MTT assay for 72h of drug action revealed that 2-4 exhibited moderate activity in cervical human tumor cells (HeLa). Complex 2 exhibited low activity in colon cancer LS-174 cells (180 +/- 10), while all complexes were devoid of activity in lung cancer A549 and non-tumor MRC-5 cells, up to 200M. Combinational studies of the most active complex 2, with pharmacological modulators of cell redox status, L-buthionine-sulfoximine (L-BSO) or N-acetyl-L-cysteine (NAC), showed that when L-BSO potentiated, 2 induced a sub-G1 peak of the cell cycle in the HeLa cell line. UV-vis and cyclic voltammetry were performed in order to investigate the binding mode of 2 to DNA and suggested intercalation for the complex-DNA interaction. [GRAPHICS]",
journal = "Journal of Coordination Chemistry",
title = "Ruthenium(II) bipyridine complexes: from synthesis and crystal structures to electrochemical and cytotoxicity investigation",
volume = "70",
number = "5",
pages = "831-847",
doi = "10.1080/00958972.2017.1282611"
}

Baroud, A. A., Mihajlović-Lalić, L. E., Gligorijević, N. N., Aranđelović, S., Stanković, D. M., Radulović, S. S., Van Hecke, K., Savić, A.,& Grgurić-Šipka, S.. (2017). Ruthenium(II) bipyridine complexes: from synthesis and crystal structures to electrochemical and cytotoxicity investigation. in Journal of Coordination Chemistry, 70(5), 831-847.
https://doi.org/10.1080/00958972.2017.1282611

Baroud AA, Mihajlović-Lalić LE, Gligorijević NN, Aranđelović S, Stanković DM, Radulović SS, Van Hecke K, Savić A, Grgurić-Šipka S. Ruthenium(II) bipyridine complexes: from synthesis and crystal structures to electrochemical and cytotoxicity investigation. in Journal of Coordination Chemistry. 2017;70(5):831-847.
doi:10.1080/00958972.2017.1282611 .

Baroud, Afya A., Mihajlović-Lalić, Ljiljana E., Gligorijević, Nevenka N., Aranđelović, Sandra, Stanković, Dalibor M., Radulović, Siniša S., Van Hecke, Kristof, Savić, Aleksandar, Grgurić-Šipka, Sanja, "Ruthenium(II) bipyridine complexes: from synthesis and crystal structures to electrochemical and cytotoxicity investigation" in Journal of Coordination Chemistry, 70, no. 5 (2017):831-847,
https://doi.org/10.1080/00958972.2017.1282611 . .

TY  - JOUR
AU  - Srdić-Rajić, Tatjana
AU  - Nikolić, Katarina M.
AU  - Čavić, Milena R.
AU  - Đokić, Ivana
AU  - Gemović, Branislava S.
AU  - Perović, Vladimir R.
AU  - Veljković, Nevena V.
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/884
AB  - Imidazoline I1 receptor signaling is associated with pathways that regulate cell viability leading to varied cell-type specific phenotypes. We demonstrated that the antihypertensive drug rilmenidine, a selective imidazoline I1 receptor agonist, modulates proliferation and stimulates the proapoptotic protein Bax thus inducing the perturbation of the mitochondrial pathway and apoptosis in human leukemic K562 cells. Rilmenidine acts through a mechanism which involves deactivation of Ras/MAP kinases ERK, p38 and JNK. Moreover, rilmenidine renders K562 cells, which are particularly resistant to chemotherapeutic agents, susceptible to the DNA damaging drug doxorubicin. The rilmenidine co-treatment with doxorubicin reverses G2/M arrest and triggers apoptotic response to DNA damage. Our data offer new insights into the pathways associated with imidazoline I1 receptor activation in K562 cells suggesting rilmenidine as a valuable tool to deepen our understanding of imidazoline I1 receptor signaling in hematologic malignancies and to search for medicinally active agents. (C) 2015 Elsevier B.V. All rights reserved.
PB  - Elsevier
T2  - European Journal of Pharmaceutical Sciences
T1  - Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells
VL  - 81
SP  - 172
EP  - 180
DO  - 10.1016/j.ejps.2015.10.017
ER  - 

@article{
author = "Srdić-Rajić, Tatjana and Nikolić, Katarina M. and Čavić, Milena R. and Đokić, Ivana and Gemović, Branislava S. and Perović, Vladimir R. and Veljković, Nevena V.",
year = "2016",
abstract = "Imidazoline I1 receptor signaling is associated with pathways that regulate cell viability leading to varied cell-type specific phenotypes. We demonstrated that the antihypertensive drug rilmenidine, a selective imidazoline I1 receptor agonist, modulates proliferation and stimulates the proapoptotic protein Bax thus inducing the perturbation of the mitochondrial pathway and apoptosis in human leukemic K562 cells. Rilmenidine acts through a mechanism which involves deactivation of Ras/MAP kinases ERK, p38 and JNK. Moreover, rilmenidine renders K562 cells, which are particularly resistant to chemotherapeutic agents, susceptible to the DNA damaging drug doxorubicin. The rilmenidine co-treatment with doxorubicin reverses G2/M arrest and triggers apoptotic response to DNA damage. Our data offer new insights into the pathways associated with imidazoline I1 receptor activation in K562 cells suggesting rilmenidine as a valuable tool to deepen our understanding of imidazoline I1 receptor signaling in hematologic malignancies and to search for medicinally active agents. (C) 2015 Elsevier B.V. All rights reserved.",
publisher = "Elsevier",
journal = "European Journal of Pharmaceutical Sciences",
title = "Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells",
volume = "81",
pages = "172-180",
doi = "10.1016/j.ejps.2015.10.017"
}

Srdić-Rajić, T., Nikolić, K. M., Čavić, M. R., Đokić, I., Gemović, B. S., Perović, V. R.,& Veljković, N. V.. (2016). Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells. in European Journal of Pharmaceutical Sciences
Elsevier., 81, 172-180.
https://doi.org/10.1016/j.ejps.2015.10.017

Srdić-Rajić T, Nikolić KM, Čavić MR, Đokić I, Gemović BS, Perović VR, Veljković NV. Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells. in European Journal of Pharmaceutical Sciences. 2016;81:172-180.
doi:10.1016/j.ejps.2015.10.017 .

Srdić-Rajić, Tatjana, Nikolić, Katarina M., Čavić, Milena R., Đokić, Ivana, Gemović, Branislava S., Perović, Vladimir R., Veljković, Nevena V., "Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells" in European Journal of Pharmaceutical Sciences, 81 (2016):172-180,
https://doi.org/10.1016/j.ejps.2015.10.017 . .

TY  - JOUR
AU  - Srdić-Rajić, Tatjana
AU  - Keković, Goran
AU  - Davidović, Dragomir M.
AU  - Metlaš, Radmila
PY  - 2013
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5519
AB  - A physical and mathematical model identifies similarities between phosphocholine-binding antibodies.A methodology based on the representation of each amino acid of a protein sequence by the electron-ion interaction potential and subsequent analysis by signal processing was used to determine the characteristic or common frequency (in Hz) that reflects the biological activity shared among phosphocholine (PC)-binding antibodies. The common frequency for the variable portion of the heavy chain (VH) of the PC-specific antibodies is found to be at f 0.37 Hz. The VH sequences of the PC-binding antibodies exhibit three subsites for the PC moiety where hypervariable region 2 (CDR2) plays a role in the interaction with the phosphate group. Mutations in this VH region have an impact on the ability of mutant variants to bind PC and its carrier molecule, as well as on the characteristic frequency shift toward f 0.12 Hz for mutants failing to bind both hapten and carrier. The VH sequence of mutants that retain the ability to bind PC still shows f 0.37 Hz, suggesting that this frequency determines PC binding. However, this statement was not confirmed as mutation in another PC subsite impairs PC binding but retains both the phosphate-group recognition and the frequency at f 0.37 Hz. Herein, this finding is discussed to promote the idea that the VH sequence of the PC-binding antibodies encodes the subsite for phosphate-group binding as a dominant functional activity and that only CDR2 of the T15-idiotype antibodies together with FR3 region form an autonomous self-association function represented by the T15VH5073 peptide with f 0.370.05 Hz. Thus, these data confirmed that T15VH50-73 peptide might be used in superantibody technology.
T2  - International Immunology
T1  - Phosphocholine-binding antibody activities are hierarchically encoded in the sequence of the heavy-chain variable region: dominance of self-association activity in the T15 idiotype
VL  - 25
IS  - 6
SP  - 345
EP  - 352
DO  - 10.1093/intimm/dxs156
ER  - 

@article{
author = "Srdić-Rajić, Tatjana and Keković, Goran and Davidović, Dragomir M. and Metlaš, Radmila",
year = "2013",
abstract = "A physical and mathematical model identifies similarities between phosphocholine-binding antibodies.A methodology based on the representation of each amino acid of a protein sequence by the electron-ion interaction potential and subsequent analysis by signal processing was used to determine the characteristic or common frequency (in Hz) that reflects the biological activity shared among phosphocholine (PC)-binding antibodies. The common frequency for the variable portion of the heavy chain (VH) of the PC-specific antibodies is found to be at f 0.37 Hz. The VH sequences of the PC-binding antibodies exhibit three subsites for the PC moiety where hypervariable region 2 (CDR2) plays a role in the interaction with the phosphate group. Mutations in this VH region have an impact on the ability of mutant variants to bind PC and its carrier molecule, as well as on the characteristic frequency shift toward f 0.12 Hz for mutants failing to bind both hapten and carrier. The VH sequence of mutants that retain the ability to bind PC still shows f 0.37 Hz, suggesting that this frequency determines PC binding. However, this statement was not confirmed as mutation in another PC subsite impairs PC binding but retains both the phosphate-group recognition and the frequency at f 0.37 Hz. Herein, this finding is discussed to promote the idea that the VH sequence of the PC-binding antibodies encodes the subsite for phosphate-group binding as a dominant functional activity and that only CDR2 of the T15-idiotype antibodies together with FR3 region form an autonomous self-association function represented by the T15VH5073 peptide with f 0.370.05 Hz. Thus, these data confirmed that T15VH50-73 peptide might be used in superantibody technology.",
journal = "International Immunology",
title = "Phosphocholine-binding antibody activities are hierarchically encoded in the sequence of the heavy-chain variable region: dominance of self-association activity in the T15 idiotype",
volume = "25",
number = "6",
pages = "345-352",
doi = "10.1093/intimm/dxs156"
}

Srdić-Rajić, T., Keković, G., Davidović, D. M.,& Metlaš, R.. (2013). Phosphocholine-binding antibody activities are hierarchically encoded in the sequence of the heavy-chain variable region: dominance of self-association activity in the T15 idiotype. in International Immunology, 25(6), 345-352.
https://doi.org/10.1093/intimm/dxs156

Srdić-Rajić T, Keković G, Davidović DM, Metlaš R. Phosphocholine-binding antibody activities are hierarchically encoded in the sequence of the heavy-chain variable region: dominance of self-association activity in the T15 idiotype. in International Immunology. 2013;25(6):345-352.
doi:10.1093/intimm/dxs156 .

Srdić-Rajić, Tatjana, Keković, Goran, Davidović, Dragomir M., Metlaš, Radmila, "Phosphocholine-binding antibody activities are hierarchically encoded in the sequence of the heavy-chain variable region: dominance of self-association activity in the T15 idiotype" in International Immunology, 25, no. 6 (2013):345-352,
https://doi.org/10.1093/intimm/dxs156 . .

TY  - JOUR
AU  - Srdić-Rajić, Tatjana
AU  - Jurišić, Vladimir
AU  - Andrejevic, Sladjana
AU  - Bonaci-Nikolic, Branka
AU  - Bowker, Timothy
AU  - Concas, Daniela
AU  - Metlaš, Radmila
PY  - 2012
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/4657
AB  - The production of autoantibodies against a vast array of self antigens, most notably double stranded (ds) DNA, characterized systemic lupus erythematosus (SLE). The purpose of this work is to study specific Ig fractions isolated from normal human serum (NHS) and their effect on the binding of anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies (Abs) to dsDNA. A fraction named immunoglobulin G (IgG)-reactive IgG was purified from total NHS IgG by absorption onto (CNBr)-activated Sepharose 4B linked to intact IgG molecules (IgG-Sepharose column). IgG-reactive IgG was co-incubated with systemic lupus erythematosus (SLE) patients serum and binding of the anti-dsDNA Abs to dsDNA was measured by enzyme-linked immunosorbent assay (ELISA). Co-incubation of SLE patients serum with IgG-reactive IgG resulted in a dose-dependent reduction in binding of anti-dsDNA Abs to dsDNA. A reduction greater than 70% was observed at a concentration of 300 mu g of IgG-reactive IgG per mL of a 400-fold diluted SLE patients serum whereas total NHS IgG, at the same concentration, resulted in a 10% reduction in binding. The purification process used to isolate IgG-reactive IgG was based on interactions between intact Ig rather than on interactions between F(ab)(2) portions. IgG(2) is the predominant immunoglobulin (Ig) subclass in IgG-reactive IgG. Thus, IgG(2) might have an important role in the connectivity characteristics of NHS IgG. The capacity of IgG-reactive IgG to inhibit anti-DNA Ab binding to dsDNA may have potential application in the treatment of SLE. This targeted biological approach may provide an alternative strategy to immunosuppressants. (C) 2011 Elsevier GmbH. All rights reserved.
T2  - Immunobiology
T1  - Naturally occurring V region connected antibodies inhibit anti-dsDNA antibody reactivity with dsDNA
VL  - 217
IS  - 1
SP  - 111
EP  - 117
DO  - 10.1016/j.imbio.2011.07.026
ER  - 

@article{
author = "Srdić-Rajić, Tatjana and Jurišić, Vladimir and Andrejevic, Sladjana and Bonaci-Nikolic, Branka and Bowker, Timothy and Concas, Daniela and Metlaš, Radmila",
year = "2012",
abstract = "The production of autoantibodies against a vast array of self antigens, most notably double stranded (ds) DNA, characterized systemic lupus erythematosus (SLE). The purpose of this work is to study specific Ig fractions isolated from normal human serum (NHS) and their effect on the binding of anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies (Abs) to dsDNA. A fraction named immunoglobulin G (IgG)-reactive IgG was purified from total NHS IgG by absorption onto (CNBr)-activated Sepharose 4B linked to intact IgG molecules (IgG-Sepharose column). IgG-reactive IgG was co-incubated with systemic lupus erythematosus (SLE) patients serum and binding of the anti-dsDNA Abs to dsDNA was measured by enzyme-linked immunosorbent assay (ELISA). Co-incubation of SLE patients serum with IgG-reactive IgG resulted in a dose-dependent reduction in binding of anti-dsDNA Abs to dsDNA. A reduction greater than 70% was observed at a concentration of 300 mu g of IgG-reactive IgG per mL of a 400-fold diluted SLE patients serum whereas total NHS IgG, at the same concentration, resulted in a 10% reduction in binding. The purification process used to isolate IgG-reactive IgG was based on interactions between intact Ig rather than on interactions between F(ab)(2) portions. IgG(2) is the predominant immunoglobulin (Ig) subclass in IgG-reactive IgG. Thus, IgG(2) might have an important role in the connectivity characteristics of NHS IgG. The capacity of IgG-reactive IgG to inhibit anti-DNA Ab binding to dsDNA may have potential application in the treatment of SLE. This targeted biological approach may provide an alternative strategy to immunosuppressants. (C) 2011 Elsevier GmbH. All rights reserved.",
journal = "Immunobiology",
title = "Naturally occurring V region connected antibodies inhibit anti-dsDNA antibody reactivity with dsDNA",
volume = "217",
number = "1",
pages = "111-117",
doi = "10.1016/j.imbio.2011.07.026"
}

Srdić-Rajić, T., Jurišić, V., Andrejevic, S., Bonaci-Nikolic, B., Bowker, T., Concas, D.,& Metlaš, R.. (2012). Naturally occurring V region connected antibodies inhibit anti-dsDNA antibody reactivity with dsDNA. in Immunobiology, 217(1), 111-117.
https://doi.org/10.1016/j.imbio.2011.07.026

Srdić-Rajić T, Jurišić V, Andrejevic S, Bonaci-Nikolic B, Bowker T, Concas D, Metlaš R. Naturally occurring V region connected antibodies inhibit anti-dsDNA antibody reactivity with dsDNA. in Immunobiology. 2012;217(1):111-117.
doi:10.1016/j.imbio.2011.07.026 .

Srdić-Rajić, Tatjana, Jurišić, Vladimir, Andrejevic, Sladjana, Bonaci-Nikolic, Branka, Bowker, Timothy, Concas, Daniela, Metlaš, Radmila, "Naturally occurring V region connected antibodies inhibit anti-dsDNA antibody reactivity with dsDNA" in Immunobiology, 217, no. 1 (2012):111-117,
https://doi.org/10.1016/j.imbio.2011.07.026 . .