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Cisplatin, one of the most popular chemotherapeutic drugs on the market today, battles cancer by binding to DNA, and causing kinks which obstruct DNA replication and transcription. As a result, cisplatin halts cell proliferation of not only fast-dividing cancerous cells but healthy cells as well. To circumvent the shortcomings of cisplatin, the Anderson lab has synthesized a class of ruthenium (III)/ ferrocene compounds, named the RuLX series. These new hetero- multinuclear complexes may have greater selectivity between cancerous and healthy cells through a proposed synergistic mechanism of their metal centers. Previous work on these novel complexes has demonstrated that they interact with DNA and proteins, suggesting that they may share similar molecular targets as cisplatin. RNA has merged as a new molecular target for metal therapeutics not only due to its chemical similarity with DNA, but also due to its essential role in cellular function. Many metallochemotheraputics target RNA as well as other biomolecules in their mode of action.
The in vitro binding affinity of the RuLX complexes with RNA was investigated using a 504-base RNA encoding the dihydrofolate reductase enzyme. Evidence suggests that RuL2 and RuL3 have a stronger binding affinity to RNA than RuL1. Moreover, in vitro translation of the DHFR mRNA was carried out to observe the potential downstream effects of these interactions. All three complexes exhibited a dose-dependent reduction of DHFR enzyme activity. Investigations with RuL2 specifically, suggest that its inhibition of DHFR activity is likely due to the metal complex binding to RNA. Explorative controls show that RuL2 does not significantly inhibit enzyme activity or ribosomal protein activity.
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Kissai, Mildred Apollo, "Investigating the binding potential and downstream effects of ferrocene/ ruthenium (III) complexes with RNA" (2015). Senior Projects Spring 2015. 152.