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Cancer is one of the world’s deadliest and most biologically complex diseases, requiring a staggering number of treatment methods to match its manifold forms. Metallo-pharmaceutical compounds, exemplified by the Pt(II) compound cisplatin, have proven to be powerful chemotherapeutic agents that rely on the diverse chemistries of transition metals, finely tuned with ligands. Cisplatin, effective for primary tumor treatment, covalently binds to cellular DNA and RNA to induce cell death. Conversely, Ru(III) compound NAMI-A is known for its antimetastatic ability and non-DNA based modes of action. In an effort to combine the best aspects of distinct metal centers, previous work has shown compounds with both Pt(II) and Ru(III), such as the dinuclear IT127, exhibit greater degrees of interaction with nucleic acids and inhibition of cell mobility than either cisplatin or NAMI-A alone. In addition, the Ru(III)- ferrocene complex RuL2 has been shown to inhibit DNA mobility at much higher levels than normally observed for Ru(III) complexes. These observations suggest the distinct modes of nucleic acid interaction for both IT127 and RuL2. As RNA has emerged as a promising target for anticancer compounds given its central role in cell biology, the current research aims to identify and compare the absolute binding ratios of IT127, RuL2, cisplatin, and NAMI to a long (~500 base) RNA molecule, utilizing UV-Vis and ICP-OES to determine nucleotide-to-bound metal ratios. In addition, translation assays were used to determine the ability of mRNA-bound IT127, cisplatin, and NAMI-A to disrupt protein formation in vitro.
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Jain, Kyan Sager, "An Investigation of the RNA-Binding Ratios and Translation Inhibition Capacity of Herero-Multinuclear Complexes" (2016). Senior Projects Spring 2016. 70.
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