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

J Inorg Biochem. 2001 Oct;86(4):691-8. doi: 10.1016/s0162-0134(01)00225-2.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Binding Sites
  • Cisplatin / analogs & derivatives*
  • Cisplatin / chemistry*
  • Cisplatin / pharmacology
  • Cysteine / chemistry
  • DNA Adducts / chemistry
  • DNA Adducts / drug effects
  • Electrophoresis, Capillary
  • Guanosine Monophosphate / chemistry*
  • In Vitro Techniques
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Methionine / chemistry
  • Organoplatinum Compounds / chemistry*
  • Organoplatinum Compounds / pharmacology
  • Oxaliplatin
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrophotometry, Ultraviolet
  • Sulfur / chemistry

Substances

  • Antineoplastic Agents
  • DNA Adducts
  • Ligands
  • Organoplatinum Compounds
  • Oxaliplatin
  • Sulfur
  • Guanosine Monophosphate
  • Methionine
  • Cysteine
  • Cisplatin