Title
Spectroscopic Investigation of Auranofin Binding to Zinc Finger HIV-2 Nucleocapsid Peptides
Author
Maria Antonietta Castiglione Morelli, Angela Ostuni, Giorgio Matassi, Camilla Minichino, Angela Flagiello, Pietro Pucci, Alfonso Bavoso
Year
2016
Journal
Inorganica Chimica Acta
Abstract
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+.
Instrument
J-600
Keywords
Circular dichroism, Secondary structure, Ligand binding, Inorganic chemistry, Biochemistry