Reaction of Cd7-metallothionein with cis-dichlorodiammine platinum (II)

The reaction of Cd7-metallothionein with cis-dichlorodiammine platinum (II) has been examined in titration and kinetic experiments. Titrations followed by 111Cd NMR spectroscopy and analysis of cadmium and platinum in the products indicated that platinum displaced cadmium in approximate 1:1 fashion, producing Pt7-metallothionein. According to NMR analysis, the overall reaction involved cooperative exchange of platinum for 111Cd in each domain of the protein. There was a modest preference for the reaction of the drug with the Cd3-containing beta-domain of the protein. The product had an apparent molecular weight that was nearly the same as that of Cd7-metallothionein as determined by Sephadex G-75 chromatography. Kinetic analysis also supported a cooperative displacement mechanism. The reaction was biphasic; neither step could be identified solely with the reaction of one cluster as indicated by the biphasic reaction of the Cd4-containing alpha-domain with the platinum complex.