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Gold(I)-Phosphine-N-Heterocycles: Biological Activity and Specific (Ligand) Interactions on the C‑Terminal HIVNCp7 Zinc Finger

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journal contribution
posted on 2016-02-18, 17:43 authored by Camilla Abbehausen, Erica J. Peterson, Raphael E. F. de Paiva, Pedro P. Corbi, André L. B. Formiga, Yun Qu, Nicholas P. Farrell
The syntheses and the characterization by chemical analysis, 1H and 31P NMR spectroscopy, and mass spectrometry of a series of linear triphenylphosphine gold­(I) complexes with substituted N-heterocycle ligands (L), [(PPh3)­Au­(I)­(L)]+, is reported. The reaction of [(PPh3)­Au­(L)]+ (L = Cl or substituted N- heterocyclic pyridine) with the C-terminal (Cys3His) finger of HIVNCp7 shows evidence by mass spectrometry (ESI-MS) and 31P NMR spectroscopy of a long-lived {(PPh3)­Au}-S-peptide species resulting from displacement of the chloride or pyridine ligand by zinc-bound cysteine with concomitant displacement of Zn2+. In contrast, reactions with the Cys2His2 finger-3 of the Sp1 transcription factor shows significantly reduced intensities of {(PPh3)­Au} adducts. The results suggest the possibility of systematic (electronic, steric) variations of “carrier” group PR3 and “leaving” group L as well as the nature of the zinc finger in modulation of biological activity. The cytotoxicity, cell cycle signaling effects, and cellular accumulation of the series are also reported. All compounds display cytotoxicity in the micromolar range upon 96 h continuous exposure to human tumor cells. The results may have relevance for the reported inhibition of viral load in simian virus by the gold­(I) drug auranofin.

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