Cc. Cheng et Ch. Pai, SPECIFIC DISPLACEMENT OF GLUTATHIONE FROM THE PT(II)-GLUTATHIONE ADDUCT BY CU(II) IN NEUTRAL PHOSPHATE BUFFER, Journal of inorganic biochemistry, 71(3-4), 1998, pp. 109-113
The Pt-S bond of Pt(II)-glutathione (GS-Pt) complex was dissociable in
neutral phosphate buffer at room temperature in the presence of Cu(II
) ion. In addition, the chloro species, Pt(terpy)Cl+, was isolated and
identified as the major cleavage product of Pt(terpy)(GS)(2+) complex
when CuCl2 was used. The Pt-S bond dissociation of Pt(terpy)(GS)(2+)
mediated by Cu(II) ion was shown to be a pH dependent process in the r
ange of 4.5-8.0. At pH <7, MMR evidence was obtained for a S-bridged h
eterodinuclear unit formed between Pt(terpy)(GS)(2+) and the Cu(II) io
n; however, no Pt-S bond dissociation was observed up to 24 h. At pH g
reater than or equal to 7, NMR data suggested coordination of the amid
e nitrogen of GSH of Pt(terpy)(GS)(2+) to the Cu(II) ion. We propose t
hat the coordination of the amide nitrogen to the Cu(II) ion, together
with the formation of the S-bridged heterodinuclear unit, induce the
Pt-S bond dissociation in Pt(terpy)(GS)(2+). These results may be expl
oited to develop a molecular activator to regenerate the anticancer ac
tivity in cisplatin pro-drugs. (C) 1998 Elsevier Science Inc. All righ
ts reserved.