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Oxidized copper has recently gained attention as a potential therapeutic drug based on its potent redox ability to generate reactive oxygen species (ROS) which can cause oxidative damage to cellular systems. Therefore, it is important to know how Cu(II) will interact with biomolecules. Zinc fingers (ZFs) are metalloproteins that require a zinc ion to maintain structure and function. Owing to the promi- nence of ZFs in biology and because copper has similar binding characteristics as zinc, exogenous copper complexes might interact with endogenous ZFs. This thesis explores the interaction between Cu(II) and two variations of the classical ZF and a RING domain via UV-Vis and fluorescence spectroscopy. Results show that Cu(II) is reduced to Cu(I) and binds to the thiolate site of the ZF, displac- ing the Zn(II) ion. ZFs also obstruct the copper catalyzed production of ROS through copper binding. Phenanthroline, a Cu(II) stabilizing chelator, serves as a surrogate Cu(II)-drug. The Cu(II)-ligand complex increases the efficiency of ROS production in the presence of ZFs relative to free Cu(II) ions. This could suggest the stabilized ligand complex prevents the copper from immediately binding to ZFs and becoming redox silenced. Collectively, these results show that ZFs might be considered a potential target for Cu(II) drugs.
Rodemeier, Madeline E., "Copper(II) Interaction with Zinc Fingers: Feasibility of Copper(II)-based Drugs" (2022). Chemistry Honors Projects. 34.
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