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Alumna Authors JOC Cover Article

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Judy Zhu (HBS ’15) is first author on the current cover article of The Journal of Organic Chemistry. The paper is based on her undergraduate honors thesis, covering the pH dependency of 5-guanidinohydantoin, important in research around DNA damage and resulting diseases.

Judy is currently spending a gap year in Cindy Burrows‘ lab, then plans to pursue an MD, PhD, or both. Congratulations Judy!

Judy Zhu stands outside in front of a brick wall. She has long dark hair around her shoulders and is wearing a white sweater and jeans. She is holding the cover of the Journal of Organic Chemistry, which shows an illustration of a snowy slope with two ski tracks that diverge into two DNA strands, one red and one blue. Around the DNA strands are structures of the molecules studied in Zhu's paper.Abstract:

Four-electron oxidation of 2′-deoxyguanosine (dG) yields 5-guanidinohydantoin (dGh) as a product. Previously, we hypothesized that dGh could isomerize to iminoallantoin (dIa) via a mechanism similar to the isomerization of allantoin. The isomerization reaction was monitored by HPLC and found to be pH dependent with a transition pH = 10.1 in which dGh was favored at low pH and dIa was favored at high pH. The structures for these isomers were confirmed by UV–vis, MS, and 1H and 13C NMR. Additionally, the UV–vis and NMR experimental results are supported by density functional theory calculations. A mechanism is proposed to support the pH dependency of the isomerization reaction. Next, we noted the hydantoin ring of dGh mimics thymine, while the iminohydantoin ring of dIa mimics cytosine; consequently, a dGh/dIa site was synthesized in a DNA template strand, and standing start primer extension studies were conducted with Klenow fragment exo–. The dATP/dGTP insertion ratio opposite the dGh/dIa site as a function of pH was evaluated from pH 6.5–9.0. At pH 6.5, only dATP was inserted, but as the pH increased to 9.0, the amount of dGTP insertion steadily increased. This observation supports dGh to dIa isomerization in DNA with a transition pH of ∼8.2.

Read her full paper here: http://pubs.acs.org/doi/abs/10.1021/acs.joc.5b02180

Image shows the cover of the Journal of Organic Chemistry, which shows an illustration of a snowy slope with two ski tracks that diverge into two DNA strands, one red and one blue. Around the DNA strands are structures of the molecules studied in Zhu's paper.