USING CLICK CHEMISTRY TO MODULATE THE AGGREGATION OF THE PARKINSON’S DISEASE PROTEIN

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the presence of protein aggregates called Lewy bodies. These plaques are primarily composed of oligomers of the protein ?-synuclein (?S), which is a small protein of 140 amino acids that is natively unfolded, however the folding of this protein has been found to be accelerated in the presence of metal ions, particularly copper. One ideology that has been used for therapeutic removal of endogenous metal ions is chelation therapy. Click chemistry, or the Copper-Catalyzed Azide-Alkyne Cycloaddition (CuAAC), involves the reaction of an alkyne and an azide, resulting in the formation of a 1,2,3-substituted triazole. This reaction is well known for being extremely versatile, accommodating a wide variety of functionalized alkynes and azides. Recently,