Characterization of the binding sites of the anticancer ruthenium(III) complexes KP1019 and KP1339 on human serum albumin via competition studies.
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.
Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, Szeged 6720, Hungary.
Orsolya
O
Dömötör
Christian G
CG
Hartinger
Anna K
AK
Bytzek
Tamás
T
Kiss
Bernhard K
BK
Keppler
Eva A
EA
Enyedy
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism*; D001663:Bilirubin / Q000378:metabolism; D001667:Binding, Competitive; D006418:Heme / Q000378:metabolism; D006801:Humans; D007191:Indazoles / Q000737:chemistry / Q000378:metabolism*; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism*; D012428:Ruthenium / Q000737:chemistry*; D017975:Ruthenium Compounds; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
D000970:Antineoplastic Agents; D007191:Indazoles; C551585:KP 1339; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; D012709:Serum Albumin; C499292:indazolium trans-(tetrachlorobis(1H-indazole)ruthenate (III)); D006418:Heme; D012428:Ruthenium; D001663:Bilirubin