Interactions of ruthenium(II)-cymene complexes with cytochrome c
Аутори
Radomirović, Mirjana Ž.Stanić-Vučinić, Dragana
Nikolić, Stefan
Mihailović, Jelena
Ćirković-Veličković, Tanja
Grgurić Šipka, Sanja
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
The ruthenium-based antitumour compounds act more via protein targets involved in carcinogenesis, in contrast to platinum-based compounds. Also, after intravenous administration of antitumour complexes proteins are the first binding targets in circulation. Therefore, interactions of anticancer compounds with proteins are important for elucidation of their pharmacokinetic pathways. Four half-sandwich ruthenium(II)-cymene complexes (C1, C2, C3 and C4), developed earlier and with promising cytotoxic activity, are investigated for their interactions with cytochrome c (Cyt). Complexes were incubated with Cyt for 48 h at 37 °C and high-resolution LTQ-Orbitrap ESI MS was used to monitor the formed adducts. The changes in heme state and tertiary structure around the heme were monitored by CD and UV-VIS spectra in the presence of oxygen. The complexes containing two chloride ligands (C2 and C3) were more reactive toward Cyt than those with only one (C1 and C4). The complex with S,N-chelating l...igand (C4) was less reactive than one with O,N-chelating ligand (C1). All complexes reduced heme iron of Cyt, but the extent of reduction was inverse to the order of their reactivity to Cyt (C1>C4>>C2>C3). CD spectra in Soret region indicated that Cyt reduction was accompanied with slight tertiary structure change, the rupture of ferro-Met-80 and occupation of this heme coordination site by His-33/His-26. Extent of heme reduction by complexes inverse with respect to their reactivity implies that initially noncovalent binding of complexes occures, causing heme reduction, followed by comlex coordination to protein. In the presence of less reactive complexes more intensive reduction of heme leaves less available histidine residues (main targets for Ru coordination), leading to less efficient formation of adducts.
Извор:
1st FoodEnTwin Workshop “Food and Environmental –Omics”, Belgrade, Serbia, 20th-21st June, 2019. In: Book of Abstracts, 2019, 24-24Финансирање / пројекти:
- Молекуларне особине и модификације неких респираторних и нутритивних алергена (RS-MESTD-Basic Research (BR or ON)-172024)
- Рационални дизајн и синтеза биолошки активних и координационих једињења и функционалних материјала, релевантних у (био)нанотехнологији (RS-MESTD-Basic Research (BR or ON)-172035)
- FoodEnTwin-Twinning of research activities for the frontier research in the fields of food, nutrition and environmental omics (EU-H2020-810752)
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - CONF AU - Radomirović, Mirjana Ž. AU - Stanić-Vučinić, Dragana AU - Nikolić, Stefan AU - Mihailović, Jelena AU - Ćirković-Veličković, Tanja AU - Grgurić Šipka, Sanja PY - 2019 UR - http://cherry.chem.bg.ac.rs/handle/123456789/6037 AB - The ruthenium-based antitumour compounds act more via protein targets involved in carcinogenesis, in contrast to platinum-based compounds. Also, after intravenous administration of antitumour complexes proteins are the first binding targets in circulation. Therefore, interactions of anticancer compounds with proteins are important for elucidation of their pharmacokinetic pathways. Four half-sandwich ruthenium(II)-cymene complexes (C1, C2, C3 and C4), developed earlier and with promising cytotoxic activity, are investigated for their interactions with cytochrome c (Cyt). Complexes were incubated with Cyt for 48 h at 37 °C and high-resolution LTQ-Orbitrap ESI MS was used to monitor the formed adducts. The changes in heme state and tertiary structure around the heme were monitored by CD and UV-VIS spectra in the presence of oxygen. The complexes containing two chloride ligands (C2 and C3) were more reactive toward Cyt than those with only one (C1 and C4). The complex with S,N-chelating ligand (C4) was less reactive than one with O,N-chelating ligand (C1). All complexes reduced heme iron of Cyt, but the extent of reduction was inverse to the order of their reactivity to Cyt (C1>C4>>C2>C3). CD spectra in Soret region indicated that Cyt reduction was accompanied with slight tertiary structure change, the rupture of ferro-Met-80 and occupation of this heme coordination site by His-33/His-26. Extent of heme reduction by complexes inverse with respect to their reactivity implies that initially noncovalent binding of complexes occures, causing heme reduction, followed by comlex coordination to protein. In the presence of less reactive complexes more intensive reduction of heme leaves less available histidine residues (main targets for Ru coordination), leading to less efficient formation of adducts. C3 - 1st FoodEnTwin Workshop “Food and Environmental –Omics”, Belgrade, Serbia, 20th-21st June, 2019. In: Book of Abstracts T1 - Interactions of ruthenium(II)-cymene complexes with cytochrome c SP - 24 EP - 24 UR - https://hdl.handle.net/21.15107/rcub_cherry_6037 ER -
@conference{ author = "Radomirović, Mirjana Ž. and Stanić-Vučinić, Dragana and Nikolić, Stefan and Mihailović, Jelena and Ćirković-Veličković, Tanja and Grgurić Šipka, Sanja", year = "2019", abstract = "The ruthenium-based antitumour compounds act more via protein targets involved in carcinogenesis, in contrast to platinum-based compounds. Also, after intravenous administration of antitumour complexes proteins are the first binding targets in circulation. Therefore, interactions of anticancer compounds with proteins are important for elucidation of their pharmacokinetic pathways. Four half-sandwich ruthenium(II)-cymene complexes (C1, C2, C3 and C4), developed earlier and with promising cytotoxic activity, are investigated for their interactions with cytochrome c (Cyt). Complexes were incubated with Cyt for 48 h at 37 °C and high-resolution LTQ-Orbitrap ESI MS was used to monitor the formed adducts. The changes in heme state and tertiary structure around the heme were monitored by CD and UV-VIS spectra in the presence of oxygen. The complexes containing two chloride ligands (C2 and C3) were more reactive toward Cyt than those with only one (C1 and C4). The complex with S,N-chelating ligand (C4) was less reactive than one with O,N-chelating ligand (C1). All complexes reduced heme iron of Cyt, but the extent of reduction was inverse to the order of their reactivity to Cyt (C1>C4>>C2>C3). CD spectra in Soret region indicated that Cyt reduction was accompanied with slight tertiary structure change, the rupture of ferro-Met-80 and occupation of this heme coordination site by His-33/His-26. Extent of heme reduction by complexes inverse with respect to their reactivity implies that initially noncovalent binding of complexes occures, causing heme reduction, followed by comlex coordination to protein. In the presence of less reactive complexes more intensive reduction of heme leaves less available histidine residues (main targets for Ru coordination), leading to less efficient formation of adducts.", journal = "1st FoodEnTwin Workshop “Food and Environmental –Omics”, Belgrade, Serbia, 20th-21st June, 2019. In: Book of Abstracts", title = "Interactions of ruthenium(II)-cymene complexes with cytochrome c", pages = "24-24", url = "https://hdl.handle.net/21.15107/rcub_cherry_6037" }
Radomirović, M. Ž., Stanić-Vučinić, D., Nikolić, S., Mihailović, J., Ćirković-Veličković, T.,& Grgurić Šipka, S.. (2019). Interactions of ruthenium(II)-cymene complexes with cytochrome c. in 1st FoodEnTwin Workshop “Food and Environmental –Omics”, Belgrade, Serbia, 20th-21st June, 2019. In: Book of Abstracts, 24-24. https://hdl.handle.net/21.15107/rcub_cherry_6037
Radomirović MŽ, Stanić-Vučinić D, Nikolić S, Mihailović J, Ćirković-Veličković T, Grgurić Šipka S. Interactions of ruthenium(II)-cymene complexes with cytochrome c. in 1st FoodEnTwin Workshop “Food and Environmental –Omics”, Belgrade, Serbia, 20th-21st June, 2019. In: Book of Abstracts. 2019;:24-24. https://hdl.handle.net/21.15107/rcub_cherry_6037 .
Radomirović, Mirjana Ž., Stanić-Vučinić, Dragana, Nikolić, Stefan, Mihailović, Jelena, Ćirković-Veličković, Tanja, Grgurić Šipka, Sanja, "Interactions of ruthenium(II)-cymene complexes with cytochrome c" in 1st FoodEnTwin Workshop “Food and Environmental –Omics”, Belgrade, Serbia, 20th-21st June, 2019. In: Book of Abstracts (2019):24-24, https://hdl.handle.net/21.15107/rcub_cherry_6037 .