In vitro binding of an orally active platinum antitumor drug, JM216 to metallothionein

The in vitro binding of an orally active anticancer drug JM216 to metalloth ionein is firstly investigated in this paper. It is revealed that a redox r eaction following a substitution reaction from JM216 with rabbit liver Zn7M T-II is presented. The reaction feature, the metal binding stoichiometry an d the oxidation states of platinum and sulfur in the products are studied b y UV-visible, chromatography and X-ray photoelectron spectroscopy methods. Parts of MT are oxidized to precipitate products with intra and intermolecu lar CyS-SCy disulfides linkages. Pt(IV) is reduced to its Pt(II) counterpar t. And the reduced Pt(II) replace the metal ions in native MTs. Meanwhile i t can also cause the dimerization of MT. Increasing the reaction ratio of J M216 to MT leads to a concomitant increase in the apparent yield of the pre cipitate and dimeric products and the elevation of the binding stoichiometr y of Pt to the protein. Based on the experimental data, the reaction mechan ism between JM216 and Zn7MT-II in vitro are discussed.