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

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.