Spectroscopic investigation of auranofin binding to zinc finger HIV-2 nucleocapsid peptides

The nucleocapsidic protein (NC) of orthoretroviruses has been considered as a promising target for antiretroviral drugs. Compounds, including zinc ejectors and metal derivatives capable to substitute the zinc ion in the nucleocapsidic zinc fingers, have been described. Auranofin, a gold(I) drug used for the treatment of rheumatoid arthritis, restricts the viral reservoir in the monkey AIDS model and induces containment of viral load following anti-retroviral therapy suspension. Here is reported a study of the interactions of auranofin with two synthetic CCHC-type peptides corresponding to the C-terminal zinc finger of the HIV-2 NC protein from two different isolates, using spectroscopic techniques and mass spectrometry. Both apopeptides interact very slowly with auranofin forming an Au-peptide complex. In contrast, as shown by mass spectrometry, the zinc-bound peptides interact on a shorter time-scale by forming an Et3P-Au-peptide complex and an Au-peptide complex. The two peptides show kinetic differences in the formation of zinc complexes, in Zn2+ binding constants as well in Zn2+ displacement by Au+.