The reaction of dichlorodiammineplatinum(II), [PtCl2(NH3)2], isomers with zinc fingers

• Cis and trans-[PtCl2(NH3)2] differ in reactivity toward the HIVNCp7 C-terminal zinc finger (ZF2).
• Reaction occurs with Zn ejection.
• Mass Spectrometry shows initial formation of {Pt/Zn} and {Pt(NH3)2/Zn} peptides.
• The MS2 of the {Pt(NH3)2/Zn} peptide shows NH3 loss with retention of Pt/Zn construct.
• {1H, 15N} HSQC NMR Spectroscopy confirms Pt-S (from ZF2) bond formation.

The interaction of cis-DDP and trans-DDP (DDP = [PtCl2(NH3)2]) with the C-terminal zinc finger (ZF2) of the HIVNCp7 nucleocapsid protein was investigated by fluorescence, circular dichroism, mass spectrometry, and {1H, 15N} HSQC (heteronuclear single quantum coherence) NMR spectroscopy. The rate of reaction differed significantly for the two compounds, with the trans isomer reacting in a significantly faster manner, as expected. {1H, 15N} HSQC NMR of 15N-labeled compounds with the ZF2 showed the appearance of several new 15N peaks, consistent with sulfur binding and formation of Pt-S species. Mass spectrometry confirmed the formation of several different Pt-apopeptide/ZF2 adducts. Circular dichroism and fluorescence spectroscopy also indicated conformational changes upon binding while a 33% decrease in fluorescence of the unique tryptophan residue was seen in 72 h upon complexation of the cis isomer, while the trans isomer quenched 50% in just 24 h.

The interaction of cis-DDP and trans-DDP with the C-terminal zinc finger (ZF2) of the HIVNCp7 nucleocapsid protein is influenced by the nature of the isomer. Complementary spectroscopic techniques confirmed the formation of several different Pt-apopeptide/ZF2 adducts with formation of PtCys(S) species.Figure optionsDownload as PowerPoint slide