Probing the HIV-1 NCp7 Nucleocapsid Protein with Site-Specific Gold(I)–Phosphine Complexes

In this work, we examined a series of thiophilic Au(I) compounds based on [Au(L)(PR3)] (L = Cl–, 4-dimethylaminopyridine (dmap); R= ethyl (Et), cyclohexyl (Cy)) for chemoselective auration of the C-terminal HIV nucleocapsid protein NCp7 F2 and the “full” HIV NCp7 (NC, zinc finger (ZnF)) as probes of nucleocapsid topography. The choice of phosphine allowed electronic and steric effects to be considered. The use of the heterocycle “leaving group” allowed us to study the effect of possible π-stacking with the essential tryptophan residue of NC on the reactivity and selectivity, mimicking the naturally occurring interaction between the zinc finger and nucleic acids. We also examined for comparison the “standard” gold–phosphine compound auranofin, which contains an S-bound glucose coordinated to the {Au(PEt3)} moiety. Both the nature of the phosphine and the nature of L affect the reactivity with the C-terminal NCp7 F2 and the “full” NC. 31P NMR spectroscopy showed the formation of long-lived {Au(PR3)}–ZnF spe...