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

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 {H-1, N-15} 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. {H-1, N-15} HSQC NMR of N-15-labeled compounds with the ZF2 showed the appearance of several new N-15 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. (C) 2014 Elsevier Inc. All rights reserved.