REACTION OF CD-7-METALLOTHIONEIN WITH CIS-DICHLORODIAMINE PLATINUM(II)

The reaction of Cd-7-metallothionein with cis-dichlorodiammine platinu m (II) has been examined in titration and kinetic experiments. Titrati ons followed by Cd-111 MMR spectroscopy and analysis of cadmium and pl atinum in the products indicated that platinum displaced cadmium in ap proximate 1:1 fashion, producing Pt-7-metallothionein. According to NM R analysis, the overall reaction involved cooperative exchange of plat inum for Cd-111 in each domain of the protein. There was a modest pref erence for the reaction of the drug with the Cd,containing P-domain of the protein. The product had an apparent molecular weight that was ne arly the same as that of Cd-7-metallothionein as determined by Sephade x G-75 chromatography. Kinetic analysis also supported a cooperative d isplacement mechanism. The reaction was biphasic; neither step could b e identified solely with the reaction of one cluster as indicated by t he biphasic reaction of the Cd-4-containing alpha-domain with the plat inum complex.