Selective Targeting of the Zinc Finger Domain of HIV Nucleocapsid Protein NCp7 with Ruthenium Complexes.

Nucleocapsid protein 7 (NCp7) is an attractive target for anti-HIV drug development. Here we found that ruthenium complexes are reactive to NCp7 and various Ru-agents exhibit significantly different reactivity. Interestingly, the zinc-finger domains of NCp7 also demonstrate different affinity to Ru-complexes; the C-terminal domain is much more reactive than the N-terminal domain. Each zinc-finger domain of NCp7 binds up to three Ru-motifs, and the ruthenium binding causes zinc-ejection from NCp7 and disrupts the protein folding. Therefore, ruthenium complexes interfere with the DNA binding of NCp7 and interrupt the protein function. The different reactivity of Ru-agents suggests a feasible strategy for improving the targeting of NCp7 by ligand design. This work provides an insight into the mechanism of ruthenium complex with NCp7, and suggests more potential application of ruthenium drugs.