Aggregation of γ-globulin by cis-diamminedichloroplatinum(II): Alteration of Fc region and restoration by diethyldithiocarbamate

Abstract

Human γ-globulin containing IgGs generally shows a binding ability to protein A through its Fc region. When purified human γ-globulin was incubated with cis-diamminedichloroplatinum(II) ( cis-DDP), reduced binding to protein A was observed. On the other hand, γ-globulin in human plasma showed only a slight decrease in protein A binding at similar doses, due probably to other internal substances in plasma by trapping cis-DDP. Reduction of γ-globulin pretreated with cis-DDP resulted in significantly decreased amounts of the H and HL components, whereas the L chain was normally detected. These results suggest that cis-DDP affects the disulfide(S-S) bond(s) in the inter H-H chains which locate in the Fc region. We have demonstrated that cis-DDP causes y-globulin polymerization and its S-S bond cleavage (Chen et al., Int. J. Pharm., 106 (1994) 249–253). Diethyldithiocarbamate (DDTC) partly restored these effects of cis-DDP on γ-globulin in terms of the decreased S-S bonds, polymerization, and the reduced binding ability of y-globulin to protein A. Since DDTC is known to easily cleave the Pt-S bond, Pt-S bonds are likely to be responsible for the restoration of this γ-globulin- cis-DDP interaction.