Endogenous metabolism, environmental exposure, and treatment with some chemotherapeutic agents can give rise to DNA alkylation, which can occur on the phosphate backbone, forming alkylphosphotriester (PTE). Among the alkylated DNA lesions, PTEs were previously shown to display the longest life-time in cells, suggesting that they could be used as biomarkers for monitoring the long-term exposure to alkylating reagents and they are resistant to DNA repair. However, not much is known about how the PTE lesions compromise the efficiency and fidelity of cellular DNA replication. In the present study, we synthesized oligodeoxyribonucleotides (ODNs) containing a site-specifically inserted alkylphosphotriester, with the alkyl group being a methyl, ethyl, n-propyl, i-propyl and n-butyl. We further characterized the identities of these ODNs by using LC-MS/MS analysis. Next we will ligate these ODNs into single-stranded M13 vectors and assess how these lesions inhibit DNA replication and induce mutations during that process in Escherichia coli cells.

Chemical syntheses and characterizations of oligodeoxyribonucleotides containing site-specifically incorporated alkylphosphotriester lesions

252nd National Meeting (2016)

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