Antibiotic resistant bacteria such as methicillin resistant staph. aureus (MRSA) have proven to be deadly and present many complications in treatment. One possible alternative to traditional antibiotics is to engineer artificial nucleases designed to attack the genes of antibiotic resistant bacteria. Nucleases are enzymes that hydrolyze phosphodiester bonds in the backbone of nucleic acids. Currently there is a limited repertoire of naturally occurring nucleases with varied target binding specificities. Nucleases possess a DNA cleavage and binding domain which make them ideal for modular design. Metal ion chelates are compounds shown to possess some DNA cleavage capacity. In this study, the DNA cleavage activity of novel copper and nickel Bcyclam, Bcyclen, Bn2Cyclam, Bn2Cyclen, and Me2Cyclam complexes was measured under different conditions. Fe-EDTA, a metal complex known to hydrolyze DNA, was used as a control. Reactions with these copper and nickel compounds in the presence and absence of hydrogen peroxide both yielded hydrolysis products of the plasmid pUC19. It is apparent that an oxidative mechanism in the presence of peroxide seems to be favored possibly due to increased longevity of the overall reaction. Currently, nickel compounds have shown more consistent activity when compared to copper compounds. Work is in progress to incorporate a specific DNA binding domain with the metal complexes to target specific sequences for cleavage using TAL effectors. Future directions include investigating the target specificity of the metal complexes with and without a separate DNA binding domain.

Copper and nickel complexes as DNA cleavage components for use in artificial nucleases

251st National Meeting (2016)

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