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The Anderson lab has recently synthesized a new class of hetero-multinuclear anti-cancer compounds that seeks to circumvent the drawbacks of cisplatin, the most popular chemotherapeutic drug on the market today. These complexes have great potential for targeted ligand design and synergistic action. Previous work has demonstrated that both platinum (II)/ ruthenium (III) complexes and ruthenium(III)/ ferrocene complexes interact with DNA, suggesting that DNA may be the molecular target of these compounds.
By determining the exact sites where these hetero-multinuclear complexes bind to a 192- basepair fragment of the Tetrahymena genome, their mode of action can be determined. The platinum (II)/ruthenium (III) complexes AH197 and IT127 have previously exhibited binding affinity to plasmid DNA and the ability to terminate DNA polymerization. However no binding sequence specificity has been unequivocally demonstrated. The RuLX compounds, which feature both ruthenium (III) and iron (II) centers, have also demonstrated binding affinity to plasmid DNA, particularly in comparison to their isolated metal centers. However, their exact mode of binding remains unknown. The binding sites of each complex were mapped using both the TAQ and T4 DNA polymerase primer extension methods and radiolabeled primer. Cisplatin and both platinum (II)/ruthenium (III) complexes demonstrated termination of polymerization, as well as some preference for sequential purines. However the RuLX complexes demonstrated a general inhibition of DNA polymerase, but no site-specific binding.
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Hoque, Nushrat Jahan, "Investigating Binding Site Specificity of Hetero-multinuclear Organometallic Complexes to DNA" (2014). Senior Projects Spring 2014. 299.
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