Date of Submission

Spring 2016

Academic Programs and Concentrations

Chemistry

Project Advisor 1

Swapan Jain

Abstract/Artist's Statement

RuL2 is a potentially new inorganic anti-cancer drug that contains both Ruthenium (III) & Iron (II) metal centers. The synergistic action of the two metal centers has the potential to combine the therapeutic effects of current drugs, Cisplatin and NAMI-A, and could potentially increase the overall efficacy of the drug. Previous work on RuL2 has demonstrated that it interacts with DNA and RNA, suggesting that it may share similar molecular targets as Cisplatin. RNA has emerged as our molecular target for metal therapeutics not only due to its chemical similarity with DNA, but also due to its essential role in cellular function.

My project centered on a main question: what is the binding strength of RuL2 to RNA? How does its binding strength compare to Cisplatin and NAMI-A? The in vitro binding affinity of Cisplatin, NAMI-A, and RuL2 complexes with RNA was investigated using DHFR enzyme activity assay, and electrophoretic mobility shift assay (EMSA). The in vitro translation studies using DHFR assay showed that all three complexes inhibited the enzymatic activity of DHFR in catalyzing dihydrofolic acid to tetrahydrofolic acid, as the concentrations of drugs were increasing. On the other hand, electrophoretic mobility shift assay (EMSA) studies using SRL RNA incubated with Cisplatin, NAMI-A, and RuL2 indicated a concentration-dependent tendency for the RNA sample to migrate in increasingly diffuse streaks. So we can conclude that Cisplatin, NAMI-A, and RuL2 are all interacting with RNA. The accurate binding location and ration of each drug to RNA can be further investigated by running reverse transcriptase and ICP-OES assays, respectively.

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