Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3B (APOBEC3B, A3B) catalyzes cytosine-to-uracil (C-to-U) deamination in single-stranded (ss)DNA. A3B is overexpressed in various cancer types and is a source of genomic mutations that result in tumor evolution, and ultimately, resistance to some drug therapies. Recently, a co-crystal structure of A3B with a ssDNA substrate has been solved; indicating a tyrosine, Tyr315, near the active site of A3B is in close proximity to C5 of the target cytosine in ssDNA. We have hypothesized that a nucleoside probe bearing a sulfonyl fluoride functionality at C5 could undergo nucleophilic attack by Tyr315 using the Sulfur Fluoride Exchange (SuFEx) click reaction resulting in the formation of an A3B-ssDNA covalent adduct. In order to deliver the sulfonyl fluoride to the active site of A3B, we propose incorporating a nucleoside analogue containing this functional group into a short ssDNA strand with a sequence known to bind to A3B. Once formed, a variety of A3B-enzymatic assays will be used to characterize our new chemical probe. This poster will highlight our efforts in the development and synthesis of a ssDNA SuFEx probe for A3B.

Towards the synthesis of ssDNA-based SuFEx probes targeting APOBEC3B DNA cytosine deaminase

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.