Characterization of the binding sites of the anticancer ruthenium(III) complexes KP1019 and KP1339 on human serum albumin via competition studies
- Author(s)
- Orsolya Domotor, Christian G. Hartinger, Anna Bytzek, Tamas Kiss, Bernhard Keppler, Eva Anna Enyedy
- 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.
- Organisation(s)
- Department of Inorganic Chemistry
- External organisation(s)
- University of Szeged, University of Auckland
- Journal
- Journal of Biological Inorganic Chemistry
- Volume
- 18
- Pages
- 9-17
- No. of pages
- 9
- ISSN
- 0949-8257
- DOI
- https://doi.org/10.1007/s00775-012-0944-6
- Publication date
- 2013
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 104004 Chemical biology
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/7b96b249-7160-413f-ac47-30dda1bc5145