Na/K-ATPase as a target for anticancer metal based drugs: insights into molecular interactions with selected gold(III) complexes
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2017
Authors
Bondžić, Aleksandra M.
Janjić, Goran

Dramićanin, Miroslav

Messori, Luigi
Massai, Lara
Parac-Vogt Tatjana

Vasić, Vesna M.

Article (Published version)

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Na/K-ATPase is emerging as an important target for a variety of anticancer metal-based drugs. The interactions of Na/K-ATPase (in its E1 state) with three representative and structurally related cytotoxic gold(III) complexes, i.e. [Au(bipy)(OH)(2)][PF6], bipy = 2,2'-bipyridine; [Au(py(dmb)-H)(CH3COO)(2)], py(dmb)-H = deprotonated 6-(1,1-dimethylbenzyl)-pyridine and [Au(bipy(dmb)-H)(OH)][PF6], bipy(c)-H = deprotonated 6-(1,1-dimethylbenzyl)-2,20-bipyridine, are investigated here in depth using a variety of spectroscopic methods, in combination with docking studies. Detailed information is gained on the conformational and structural changes experienced by the enzyme upon binding of these gold(III) complexes. The quenching constants of intrinsic enzyme fluorescence, the fraction of Trp residues accessible to gold(III) complexes and the reaction stoichiometries were determined in various cases. Specific hypotheses are made concerning the binding mode of these gold(III) complexes to the enz...yme and the likely binding sites. Differences in their binding behaviour toward Na/K-ATPase are explained on the ground of their distinctive structural features. The present results offer further support to the view that Na/K-ATPase may be a relevant biomolecular target for cytotoxic gold(III) compounds of medicinal interest and may thus be involved in their overall mode of action.
Source:
Metallomics, 2017, 9, 3, 292-300Publisher:
- Royal Soc Chemistry, Cambridge
Funding / projects:
- Studies of enzyme interactions with toxic and pharmacologically active molecules (RS-172023)
- Beneficentia Stiftung (Vaduz, Liechtenstein)
- AIRC - IG-16049
- ITT
- Fondazione CRF
- CIRCMSB
DOI: 10.1039/c7mt00017k
ISSN: 1756-5901
PubMed: 28181616
WoS: 000397438600009
Scopus: 2-s2.0-85024877237
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IHTMTY - JOUR AU - Bondžić, Aleksandra M. AU - Janjić, Goran AU - Dramićanin, Miroslav AU - Messori, Luigi AU - Massai, Lara AU - Parac-Vogt Tatjana AU - Vasić, Vesna M. PY - 2017 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/2179 AB - Na/K-ATPase is emerging as an important target for a variety of anticancer metal-based drugs. The interactions of Na/K-ATPase (in its E1 state) with three representative and structurally related cytotoxic gold(III) complexes, i.e. [Au(bipy)(OH)(2)][PF6], bipy = 2,2'-bipyridine; [Au(py(dmb)-H)(CH3COO)(2)], py(dmb)-H = deprotonated 6-(1,1-dimethylbenzyl)-pyridine and [Au(bipy(dmb)-H)(OH)][PF6], bipy(c)-H = deprotonated 6-(1,1-dimethylbenzyl)-2,20-bipyridine, are investigated here in depth using a variety of spectroscopic methods, in combination with docking studies. Detailed information is gained on the conformational and structural changes experienced by the enzyme upon binding of these gold(III) complexes. The quenching constants of intrinsic enzyme fluorescence, the fraction of Trp residues accessible to gold(III) complexes and the reaction stoichiometries were determined in various cases. Specific hypotheses are made concerning the binding mode of these gold(III) complexes to the enzyme and the likely binding sites. Differences in their binding behaviour toward Na/K-ATPase are explained on the ground of their distinctive structural features. The present results offer further support to the view that Na/K-ATPase may be a relevant biomolecular target for cytotoxic gold(III) compounds of medicinal interest and may thus be involved in their overall mode of action. PB - Royal Soc Chemistry, Cambridge T2 - Metallomics T1 - Na/K-ATPase as a target for anticancer metal based drugs: insights into molecular interactions with selected gold(III) complexes VL - 9 IS - 3 SP - 292 EP - 300 DO - 10.1039/c7mt00017k ER -
@article{ author = "Bondžić, Aleksandra M. and Janjić, Goran and Dramićanin, Miroslav and Messori, Luigi and Massai, Lara and Parac-Vogt Tatjana and Vasić, Vesna M.", year = "2017", abstract = "Na/K-ATPase is emerging as an important target for a variety of anticancer metal-based drugs. The interactions of Na/K-ATPase (in its E1 state) with three representative and structurally related cytotoxic gold(III) complexes, i.e. [Au(bipy)(OH)(2)][PF6], bipy = 2,2'-bipyridine; [Au(py(dmb)-H)(CH3COO)(2)], py(dmb)-H = deprotonated 6-(1,1-dimethylbenzyl)-pyridine and [Au(bipy(dmb)-H)(OH)][PF6], bipy(c)-H = deprotonated 6-(1,1-dimethylbenzyl)-2,20-bipyridine, are investigated here in depth using a variety of spectroscopic methods, in combination with docking studies. Detailed information is gained on the conformational and structural changes experienced by the enzyme upon binding of these gold(III) complexes. The quenching constants of intrinsic enzyme fluorescence, the fraction of Trp residues accessible to gold(III) complexes and the reaction stoichiometries were determined in various cases. Specific hypotheses are made concerning the binding mode of these gold(III) complexes to the enzyme and the likely binding sites. Differences in their binding behaviour toward Na/K-ATPase are explained on the ground of their distinctive structural features. The present results offer further support to the view that Na/K-ATPase may be a relevant biomolecular target for cytotoxic gold(III) compounds of medicinal interest and may thus be involved in their overall mode of action.", publisher = "Royal Soc Chemistry, Cambridge", journal = "Metallomics", title = "Na/K-ATPase as a target for anticancer metal based drugs: insights into molecular interactions with selected gold(III) complexes", volume = "9", number = "3", pages = "292-300", doi = "10.1039/c7mt00017k" }
Bondžić, A. M., Janjić, G., Dramićanin, M., Messori, L., Massai, L., Parac-Vogt Tatjana,& Vasić, V. M.. (2017). Na/K-ATPase as a target for anticancer metal based drugs: insights into molecular interactions with selected gold(III) complexes. in Metallomics Royal Soc Chemistry, Cambridge., 9(3), 292-300. https://doi.org/10.1039/c7mt00017k
Bondžić AM, Janjić G, Dramićanin M, Messori L, Massai L, Parac-Vogt Tatjana, Vasić VM. Na/K-ATPase as a target for anticancer metal based drugs: insights into molecular interactions with selected gold(III) complexes. in Metallomics. 2017;9(3):292-300. doi:10.1039/c7mt00017k .
Bondžić, Aleksandra M., Janjić, Goran, Dramićanin, Miroslav, Messori, Luigi, Massai, Lara, Parac-Vogt Tatjana, Vasić, Vesna M., "Na/K-ATPase as a target for anticancer metal based drugs: insights into molecular interactions with selected gold(III) complexes" in Metallomics, 9, no. 3 (2017):292-300, https://doi.org/10.1039/c7mt00017k . .