The interaction of platinum-based drugs with native biologically relevant proteins.
This study focuses on the identification of the products that are formed upon binding of therapeutically relevant platinum complexes to proteins like β-lactoglobulin A (LGA), human serum albumin (HSA), or human hemoglobin (HB). The respective proteins were incubated with the platinum-based anticancer drugs cisplatin, carboplatin, and oxaliplatin. LGA was selected as the model protein in addition to the two most abundant blood proteins HSA and HB. In case of the model protein, the effect of free thiol groups on the affinity of cisplatin, carboplatin, and oxaliplatin was investigated by means of liquid chromatography electrospray ionization time-of-flight mass spectrometry (LC/ESI-ToF-MS). The reduced form of LGA, which contains four free thiol groups more than the native LGA, shows a much higher affinity to the platinum-based drugs. By means of liquid chromatography coupled to inductively coupled plasma mass spectrometry, the reaction behavior of the platinum-based drugs towards HSA and HB was investigated under different conditions considering the chloride concentration (4 or 100 mM) and the incubation time (24 and 48 h). In case of carboplatin, less than 6 % protein-bound platinum was detected. However, both cisplatin and oxaliplatin display a high affinity to the proteins investigated. Further information was obtained by means of LC/ESI-ToF-MS. In case of oxaliplatin, the complex [Pt(DACH)](2+) (DACH=C(6)N(2)H(14)) was identified interacting with HSA and HB. For cisplatin, different results were observed for the two proteins. The complex [Pt(NH(3))(2)Cl](+) interacted predominantly with HSA and [Pt(NH(3))(2)](2+) with HB.
Institute of Inorganic and Analytical Chemistry, University of Münster, Corrensstr. 28/30, 48149 Münster, Germany.
Christine
C
Brauckmann
Christoph A
CA
Wehe
Michael
M
Kieshauer
Claudia
C
Lanvers-Kaminsky
Michael
M
Sperling
Uwe
U
Karst
D000970:Antineoplastic Agents / Q000097:blood*; D016190:Carboplatin / Q000097:blood*; D002853:Chromatography, Liquid; D002945:Cisplatin / Q000097:blood*; D006454:Hemoglobins / Q000737:chemistry*; D006801:Humans; D007782:Lactoglobulins / Q000097:blood*; D009944:Organoplatinum Compounds / Q000097:blood*; D000077150:Oxaliplatin; D010084:Oxidation-Reduction; D010984:Platinum / Q000032:analysis; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry*; D012965:Sodium Chloride / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000970:Antineoplastic Agents; D006454:Hemoglobins; D007782:Lactoglobulins; D009944:Organoplatinum Compounds; D012709:Serum Albumin; D000077150:Oxaliplatin; D012965:Sodium Chloride; D010984:Platinum; D016190:Carboplatin; D002945:Cisplatin