Artículos de revistas
Gold(i)-phosphine-n-heterocycles: Biological Activity And Specific (ligand) Interactions On The C-terminal Hivncp7 Zinc Finger.
Registro en:
Inorganic Chemistry. v. 52, n. 19, p. 11280-7, 2013-Oct.
1520-510X
10.1021/ic401535s
24063530
Autor
Abbehausen, Camilla
Peterson, Erica J
de Paiva, Raphael E F
Corbi, Pedro P
Formiga, André L B
Qu, Yun
Farrell, Nicholas P
Institución
Resumen
The syntheses and the characterization by chemical analysis, (1)H and (31)P 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 (31)P 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 Zn(2+). 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. 52 11280-7