Publication Date

Summer 2020

Degree Type


Degree Name

Master of Science (MS)




Laura C. Miller Conrad


Bis-epoxides, Crosslink, DNA, Interstrand, Repair

Subject Areas



DNA interstrand crosslinking is a form of lesion that affects biological processes such as DNA replication and transcription. Due to this phenomenon, interstrand crosslink (ICL) agents such as cisplatin and other platinum-based compounds find application in chemotherapy. However, ICL repair is not well understood in mammalian cells and has only been characterized thoroughly for prokaryotes such as Escherichia coli. We worked to explore the utility of bis-epoxides in the investigation of ICL repair. This involves synthesizing novel bis-epoxides that could potentially induce ICLs and test their efficacy in ICL formation using a DNA repair assay. It is known that bis-epoxides with a four-carbon backbone, such as diepoxybutane, show evidence of ICL formation. We are interested in bis-epoxides with a five-carbon backbone to introduce a functional group in the third carbon to create different analogs, which can have various functions. The syntheses of four such bis-epoxide analogs – hydroxyl, benzyl, propargyl, and PEG - are explored and described, and the efficacy of ICL formation of the benzyl analog was tested. The syntheses primarily involved the usage of sulfonylation and SN2 reactions, and the testing of the analogs was done through a DNA repair assay. The hydroxyl and benzyl analogs were successfully synthesized, and the latter is believed to cause some sort of damage to DNA but not ICLs.

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