Copper catalysed formation of copper chelators: A new approach to the treatment of Wilson’s disease

Wilson’s disease is characterized by an increased concentration of copper in the liver, which damages liver tissue and eventually leads to neurological impairment. This disease affects an estimated 1/30,000 people worldwide. Current treatments for this disease can have severe side-effects, including neurological problems in approximately 20-50 % of the patients. The goal of this thesis is to develop compounds that will strongly bind to copper to remove it from the liver. The mechanism for selectivity in binding copper over other endogenous metals (e.g, zinc and iron) is to utilize copper-activated alkyne-azide cycloaddition to couple two moderate binding moieties to form a ligand with a much greater metal-binding affinity. The HepG2 cell line was used as an in vitro model for Wilson’s disease. A methodology to evaluate the efficacy of chelators to remove copper from the cell model was developed, and tested with a series of new copper chelating compounds.