Session: Current Topics in Biological Chemistry:

Dopamine is a type of neurotransmitter that carries many important roles in the brain and body such as movement, pleasure, attention, mood, and motivation. Dopamine can be oxidized by the metal-catalyzed oxidation reactions that lead to the formation of reactive oxygen species such as aminochrome. Excess of reactive oxygen species increases the level of oxidative stress, which is considered a major contributor to a variety of neurodegenerative diseases like Parkinson’s.
In the oxidation of dopamine, tyrosinase participates in the oxidation pathway of tyrosine residue and forms reactive oxygen species such as aminochrome. Tyrosinase is a copper metal-catalyzed enzyme that oxidizes phenols into quinones. In the neurodegeneration of dopaminergic systems in Parkinson’s disease, tyrosinase enzyme oxidizes dopamine into dopamine o-quinone. Dopamine o-quinone cyclizes at physiological pH to leucoaminochrome that auto oxidizes to aminochrome. However, the subsequent steps of dopamine oxidation in a controlled way are still not characterized.
We aimed to find a copper-small molecule complex that can act effectively as tyrosinase mimic and oxidize dopamine to different quinone forms. This complex is synthesized and kept on resin beads, as the solid support allows proximity of multiple copper centers and therefore allow its function as an enzyme mimic. We synthesized and examined the oxidation of phenolic substrate by different copper(II) complexes on resin. The oxidation of phenol and Tyr containing peptides by the copper complex on beads was examined using spectroscopic techniques in phosphate buffer pH 9. Our results indicate that phenol and the peptide GYYY are oxidized to quinone forms when reacted with the copper complex. Our synthesized solid-supported copper(II) complex can therefore act as a tyrosinase mimic successfully.

Ngoc Kim Nguyen

Undergraduate Researcher, Clark University

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