Zinc finger domains as therapeutic targets for metal-based compounds – an update

Abstract

Zinc finger proteins are one of the most abundant families of proteins and present a wide range of structures and functions. The structural zinc ion provides the correct conformation to specifically recognize DNA, RNA and protein sequences. Zinc fingers have essential functions in transcription, protein degradation, DNA repair, cell migration, and others. Recently, reports on the extensive participation of zinc fingers in disease have been published. On the other hand, much information remains to be unravelled as many genomes and proteomes are being reported. A variety of zinc fingers have been identified; however, their functions are still under investigation. Because zinc fingers have identified functions in several diseases, they are being increasingly recognized as drug targets. The replacement of Zn(II) by another metal ion in zinc fingers is one of the most prominent methods of inhibition. From one side, zinc fingers play roles in the toxicity mechanisms of Ni(II), Hg(II), Cd(II) and others. From the other side, gold, platinum, cobalt, and selenium complexes are amongst the compounds being developed as zinc finger inhibitors for therapy. The main challenge in the design of therapeutic zinc finger inhibitors is to achieve selectivity. Recently, the design of novel compounds and elucidation of the mechanisms of zinc substitution have renewed the possibilities of selective zinc finger inhibition by metal complexes. This review aims to update the status of novel strategies to selectively target zinc finger domains by metal complexes.