Application of capillary electrophoresis-mass spectrometry for the investigation of the binding behavior of oxaliplatin to 5'-GMP in the presence of the sulfur-containing amino acid L-methionine

Electrophoresis. 2002 Jan;23(1):74-80. doi: 10.1002/1522-2683(200201)23:1<74::AID-ELPS74>3.0.CO;2-F.

Abstract

Capillary electrophoresis-electrospray ionization-mass spectrometry (CE-ESI-MS) has been used for investigating the influence of the sulfur containing amino acid L-methionine (L-Met) on the binding behavior of oxaliplatin (trans-R,R-diaminocyclohexane-(oxalato)platinum(II)) to 5'-GMP. L-Methionine competes with 5'-GMP for the platinum binding site and forms as well as 5'-GMP adducts with oxaliplatin. The formation of the prognosed complexes [Pt(DACH)(L-Met-S,N)]+ and [Pt(DACH)(5'-GMP)2]2- (DACH = 1,2-diaminocyclohexane) could be proved directly by using CE-ESI-MS. Furthermore, we could now bring forward proofs, that the coordination of 5'-GMP with oxaliplatin is inhibited by L-methionine and could show, that the 5'-GMP ligands of the [Pt(DACH) (5'-GMP)2]2- complex can be replaced slowly by L-methionine whereas methionine can not be replaced by GMP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / metabolism
  • Binding Sites
  • Binding, Competitive
  • Electrophoresis, Capillary
  • Guanosine Monophosphate / antagonists & inhibitors
  • Guanosine Monophosphate / chemistry*
  • Guanosine Monophosphate / metabolism
  • Ligands
  • Methionine / pharmacology*
  • Molecular Structure
  • Organoplatinum Compounds / chemistry*
  • Organoplatinum Compounds / metabolism
  • Oxaliplatin
  • Spectrometry, Mass, Electrospray Ionization / instrumentation*
  • Spectrometry, Mass, Electrospray Ionization / methods
  • Sulfur

Substances

  • Antineoplastic Agents
  • Ligands
  • Organoplatinum Compounds
  • Oxaliplatin
  • Sulfur
  • Guanosine Monophosphate
  • Methionine