Characterization of the binding sites of the anticancer ruthenium(III) complexes KP1019 and KP1339 on human serum albumin via competition studies

Orsolya Dömötör, Christian G. Hartinger, Anna K. Bytzek, T. Kiss, Bernhard K. Keppler, E. Enyedy

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Indazolium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (KP1019) and its Na+ analogue (KP1339) are two of the most prominent non-platinum antitumor metal complexes currently undergoing clinical trials. After intravenous administration, they are known to bind to human serum albumin (HSA) in a noncovalent manner. To elucidate their HSA binding sites, displacement reactions with the established site markers warfarin and dansylglycine as well as bilirubin were monitored by spectrofluorimetry, ultrafiltration-UV-vis spectrophotometry, and/or capillary zone electrophoresis. Conditional stability constants for the binding of KP1019 and KP1339 to sites I and II of HSA were determined, indicating that both Ru(III) compounds bind to both sites with moderately strong affinity (log K 1′ = 5.3-5.8). No preference for either binding site was found, and similar results were obtained for both metal complexes, demonstrating low influence of the counter ion on the binding event. Graphical abstract: [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)9-17
Number of pages9
JournalJournal of Biological Inorganic Chemistry
Volume18
Issue number1
DOIs
Publication statusPublished - Jan 2013

Fingerprint

Ruthenium
Serum Albumin
Coordination Complexes
Binding Sites
Radiation counters
Spectrophotometry
Ultrafiltration
Capillary Electrophoresis
Warfarin
Electrophoresis
Bilirubin
Intravenous Administration
Clinical Trials
Ions
KP 1339
indazolium trans-(tetrachlorobis(1H-indazole)ruthenate (III))
tetrachloridobis(1H-indazole)ruthenate(III)

Keywords

  • Albumin
  • Binding affinity
  • Fluorescence
  • Ruthenium anticancer agents
  • Site markers
  • Solution equilibrium

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

Cite this

Characterization of the binding sites of the anticancer ruthenium(III) complexes KP1019 and KP1339 on human serum albumin via competition studies. / Dömötör, Orsolya; Hartinger, Christian G.; Bytzek, Anna K.; Kiss, T.; Keppler, Bernhard K.; Enyedy, E.

In: Journal of Biological Inorganic Chemistry, Vol. 18, No. 1, 01.2013, p. 9-17.

Research output: Contribution to journalArticle

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AB - Indazolium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (KP1019) and its Na+ analogue (KP1339) are two of the most prominent non-platinum antitumor metal complexes currently undergoing clinical trials. After intravenous administration, they are known to bind to human serum albumin (HSA) in a noncovalent manner. To elucidate their HSA binding sites, displacement reactions with the established site markers warfarin and dansylglycine as well as bilirubin were monitored by spectrofluorimetry, ultrafiltration-UV-vis spectrophotometry, and/or capillary zone electrophoresis. Conditional stability constants for the binding of KP1019 and KP1339 to sites I and II of HSA were determined, indicating that both Ru(III) compounds bind to both sites with moderately strong affinity (log K 1′ = 5.3-5.8). No preference for either binding site was found, and similar results were obtained for both metal complexes, demonstrating low influence of the counter ion on the binding event. Graphical abstract: [Figure not available: see fulltext.]

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