they showed no cytotoxicity. Pyridinioalkanoyl thiolesters (PATES) N-[2-(5-pyridiniovaleroylthio)benzoyl]sulfacetamide bromide (referred to as compound 45) is a pyridinioalkanoyl thiolester that can function as a zinc ejector. Once activated with silver, compound 45 uses its pyridinioalkanoyl groups to covalently modify NCp7, specifically altering cysteines 36 and 49 on the carboxyl-terminal zinc finger. It ejects the zinc from the zinc binding sites in a two steps. The zinc in the carboxyl-terminal zinc finger is released first, followed by the ejection of zinc from the amino-terminal zinc finger. Bis-Thiadizolbenzene-1,2-Diamine Bis-Thiadizolbenzene-1,2-diamine (NV038) is one of the newer zinc ejectors. NV038 is found to effect the function of the zinc finger after the virus has entered the cell but before reverse transcription is completed. NV038, like other zinc ejector compounds, chelates zinc to remove it from its binding site. However, it is thought to act through a different mechanism than many of the other zinc ejectors due to its structural features. Its structure would not readily allow thiol-disulfide interchange or acyl transfer to cysteine. Instead, NV038 is believed to react with the zinc using its two carbonyl oxygens found in the esters. 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 essentially 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. References Molecular biology Enzyme inhibitors