Reversibility of Binding of Cisplatin-Methionine in Proteins by

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Inorg. Chem. 1990, 29, 2 11-222

Contribution from the Department of Chemistry, Gorlaeus Laboratories, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands

Reversibility of Binding of Cisplatin-Methionine in Proteins by Diethyldithiocarbamate or Thiourea: A Study with Model Adducts Edwin L. M. Lempers and Jan Reedijk* Received September 29, 1988 Model adducts for platinum-protein binding, i.e. at cysteine and methionine sites, have been synthesized by starting from [PtCl(dien)]CI, ~is-Pt(NH,)~cl~, trans-Pt(NH,),CI,, and [PtCI(NH,),]CI. Glutathione (GSH) and S-methylglutathione (GS-Me) and [PtCI(NH,),]CI form trans-Ptwere used to mimic the sulfur atoms in the proteins. At pH 11 both tran~-Pt(NH~)~Cl, (NH3)2(GS)2upon reaction with 2 equiv of GS-. Only the intermediate [Pt(NH,),GS]CI was found to be relatively stable. The could not be reversed by sodium diethyldithiocarbamate Pt-cysteine type bonds in [Pt(dien)GS]+and in tran~-Pt(NH,)~(Gs), (Na(ddtc)) and thiourea. On the other hand the Pt-methionine models [Pt(dien)GS-MeI2+and cis-Pt(GS-Me) react fast with Na(ddtc) (tIl2 =