Binding and Aggregation of Human γ-Globulin by cis-Diamminedichloroplatinum (II) through Disulfide Bond

抄録

The incubation of γ-globulin with cis-diamminedichloroplatinum (II) (cis-DDP) resulted in gradual formation of insoluble aggregates. Since the precipitate, composed of polymerized γ-globulin and cis-DDP, were completely solubilized with urea, the reaction mixture containing precipitate was examined in terms of the binding of cis-DDP and the effect on disulfide (S-S) bonds in the γ-globulin. When γ-globulin was incubated with 30 molar excess cis-DDP at pH 7.4 and 37°C, cis-DDP gradually bound to as much as 12mol per mol of γ-globulin in 14d. Concurrently, about four disulfide bonds were cleaved without reaching a certain plateau. An sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the aggregated γ-globulin induced by cis-DDP was significantly different from that of the heat-denaturated aggregate form or the reduced form by sulfitolysis. The aquated complexes of cis-DDP also produced an insoluble precipitate and affected the S-S bond to a greater extent than the parent drug.