1 research outputs found
Gold(I)-Phosphine-N-Heterocycles: Biological Activity and Specific (Ligand) Interactions on the CāTerminal HIVNCp7 Zinc Finger
The syntheses and
the characterization by chemical analysis, <sup>1</sup>H and <sup>31</sup>P NMR spectroscopy, and mass spectrometry of a series of
linear triphenylphosphine goldĀ(I) complexes with substituted N-heterocycle
ligands (L), [(PPh<sub>3</sub>)ĀAuĀ(I)Ā(L)]<sup>+</sup>, is reported.
The reaction of [(PPh<sub>3</sub>)ĀAuĀ(L)]<sup>+</sup> (L = Cl<sup>ā</sup> or substituted N- heterocyclic pyridine) with the C-terminal (Cys<sub>3</sub>His) finger of HIVNCp7 shows evidence by mass spectrometry
(ESI-MS) and <sup>31</sup>P NMR spectroscopy of a long-lived {(PPh<sub>3</sub>)ĀAu}-S-peptide species resulting from displacement of the
chloride or pyridine ligand by zinc-bound cysteine with concomitant
displacement of Zn<sup>2+</sup>. In contrast, reactions with the Cys<sub>2</sub>His<sub>2</sub> finger-3 of the Sp1 transcription factor shows
significantly reduced intensities of {(PPh<sub>3</sub>)ĀAu} adducts.
The results suggest the possibility of systematic (electronic, steric)
variations of ācarrierā group PR<sub>3</sub> and āleavingā
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 goldĀ(I)
drug auranofin