Zinc Finger Inhibitor - Safety Concerns

Safety Concerns

There was concern over whether these zinc ejectors were safe to use due to the uncertainty as to whether the zinc ejectors had sufficient selectivity to target only the CCHC binding sites of the zinc fingers in NCp7. Zinc finger domains are not unique to HIV but rather are ubiquitous in cell biology, and play important roles in many processes such as cellular replication, protein-protein interactions, and DNA replication. If these zinc ejectors unintentionally bind to the wrong zinc finger domains they have the potential to adversely affect other cellular functions that could be essential for proper bodily functions.

Experimentation and modeling of the selectivity of DIBA-1, ADA, and other zinc ejectors found that this safety concern was completely unfounded. All zinc ejectors were found to effectively combat the replication of HIV at concentrations that did not exhibit cytotoxic effects denoting that they specifically targeted NCp7 and did not target other zinc fingers. It is thought that factors such as ligand binding affinity, ligand reactive proximity, and the general saddleshape necessary for the compound to fit into the binding pocket all play a role in the selectivity shown by zinc ejectors.