Nucleic acid damage is a double-edged sword. It is involved in aging and plays a role in the etiology of diseases, such as cancer. Yet, DNA is also the target of therapeutic agents, which oxidize the biopolymer. While DNA is frequently the target of cytotoxic agents, why particular forms of damage are deleterious is often not understood. This is in part due to the indiscriminate manner in which agents chemically react with DNA and the heterogeneous structure of nucleic acids, which complicates analyzing the effects of specific forms of DNA damage.<br/><br/>Our research group utilizes organic chemistry to mimic the effects of biologically active molecules on nucleic acids by chemically synthesizing oligonucleotides containing the products and reactive species generated by these damaging agents at defined sites. Using these oligonucleotide substrates, organic chemistry, biochemistry, and molecular biology techniques are combined to elucidate how nucleic acids are damaged, what the consequences of damage are, and when opportunities arise, exploit what we have learned. By looking beneath the surface of DNA damage, we gain chemical insight into the source of the cytotoxicity of therapeutic agents. In some instances this knowledge has provided inspiration for designing molecules that possess useful biochemical properties. Recent efforts in this area will be presented.<br/>

Looking beneath the surface to determine what makes DNA damage deleterious<br />

249th National Meeting (2015)

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