Comparison of the binding behavior of oxaliplatin, cisplatin and analogues to 5'-GMP in the presence of sulfur-containing molecules by means of capillary electrophoresis and electrospray mass spectrometry.
Capillary electrophoresis as well as ESI-MS has been applied for investigating the influence of the sulfur-containing amino acids L-cysteine and L-methionine on the binding behavior of oxaliplatin (trans-R,R-diaminocyclohexane(oxalato)platinum(II)), cisplatin (cis-diamminedichloroplatinum(II)), carboplatin (cis-diammine-1,1-cyclobutanedicarboxylatoplatinum(II)), cis-diammine(malonato)platinum(II) and cis-diammine(2-hydroxymalonato)platinum(II) to 5'-GMP. The presence of L-methionine resulted in a different kind of adduct formation which involves ammine release due to the trans-effect of sulfur. In addition, the time-dependent behavior of the reaction with 5'-GMP changed significantly. Due to the high stability of the diaminocyclohexane (DACH) platinum fragment, oxaliplatin showed a completely different behavior in comparison to diammine platinum complexes. Formation of [Pt(DACH)(L-Met-S,N)](+) inhibits coordination of 5'-GMP. Displacement of L-Met by 5'-GMP does not occur. Differences concerning the mode of action of oxaliplatin are expected. Characterization of the analytes was performed by UV, NMR and mass spectrometry.
Küng
A
A
Institute of Inorganic Chemistry, University of Vienna, Waehringerstrasse 42, A-1090, Vienna, Austria.
Strickmann
D B
DB
Galanski
Mathea S
MS
Keppler
B K
BK
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D003545:Cysteine / Q000737:chemistry; D018736:DNA Adducts / Q000737:chemistry / Q000187:drug effects; D019075:Electrophoresis, Capillary; D006157:Guanosine Monophosphate / Q000737:chemistry*; D066298:In Vitro Techniques; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008715:Methionine / Q000737:chemistry; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000494:pharmacology; D000077150:Oxaliplatin; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D013455:Sulfur / Q000737:chemistry
D000970:Antineoplastic Agents; D018736:DNA Adducts; D008024:Ligands; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D013455:Sulfur; D006157:Guanosine Monophosphate; D008715:Methionine; D003545:Cysteine; D002945:Cisplatin