Zinc finger proteins as templates for metal ion exchange and ligand reactivity. Chemical and biological consequences

Abstract

Zinc finger reactions with inorganic ions and coordination compounds are as diverse as the zinc fingers themselves. Use of metal ions such as Co²⁺ and Cd²⁺ has given structural, thermodynamic and kinetic information on zinc fingers and zinc-finger-DNA/RNA interactions. It is a general truism that alteration of the coordination sphere in the finger environment will disrupt the recognition with DNA/RNA and this has implications for mechanism of toxicity and carcinogenesis of metal ions. Structural zinc fingers are susceptible to electrophilic attack and the recognition that the coordination sphere of inorganic compounds may be modulated for control of electrophilic attack on zinc fingers raises the possibility of systematic studies of zinc fingers as drug targets using inorganic chemistry. Some inorganic compounds such as those of As(III) and Au(I) may exert their biological effects through inactivation of zinc fingers and novel approaches to specifically attack the zinc-bound ligands using Co(III)-Schiff bases and Platinum(II)-Nucleobase compounds have been proposed. The genomic importance of zinc fingers suggests that the “coordination chemistry” of zinc fingers themselves is ripe for exploration to design new targets for medicinal inorganic chemistry.