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.
Strickmann
Dirk B
DB
Institute of Inorganic Chemistry, University of Vienna, Austria.
Kong
Angelika
A
Keppler
Bernhard K
BK
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive; D019075:Electrophoresis, Capillary; D006157:Guanosine Monophosphate / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008715:Methionine / Q000494:pharmacology*; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000378:metabolism; D000077150:Oxaliplatin; D021241:Spectrometry, Mass, Electrospray Ionization / Q000295:instrumentation* / Q000379:methods; D013455:Sulfur
D000970:Antineoplastic Agents; D008024:Ligands; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D013455:Sulfur; D006157:Guanosine Monophosphate; D008715:Methionine