Postdoctoral Research Associate
Durham, North Carolina, Us
Nucleotide Synthesis:Synthesized and purified α-P-borano nucleoside triphosphate (NTPαB) and diphosphate (NDPαB) analogs for use as Hepatitis C (HCV) RNA dependant RNA polymerase (RdRP) and human immunodeficiency virus reverse transcriptase (HIV-RT) inhibitors (Nucleic Acids Symposium Series (Oxf) 52(1); 81-82) Enzyme Kinetics:Successfully developed HCV RdRP assays to determine, for the first time, the potency (IC50) and steady-state kinetic inhibition constant (Ki) for antiviral NTPαB's versus the natural phosphate controls. This provided an insightful look into how replacing a non-bridging α-phosphate oxygen in an NTP with a borane group modifies the antiviral potency of chain terminating nucleotides (Antiviral Research 98(2); 144-52)Synthetic Support for Small Interfering RNA (siRNA) and RNA Aptamers:Synthesized normal NTPαBs and the 2′-Fluoro modified NTPs used by the lab to transcribe siRNA and RNA aptamers. Synthesized gemcitabine triphosphate (dFdCTP) by developing a unique method that separates gemcitabine nucleoside from the pharmaceutical excipients in the anti-cancer drug Gemzar®, directly yielding the 3’-OH, N4-NH3-protected nucleoside, that was immediately converted to a 5'-triphosphate. We then incorporated dFdCTP into an RNA oligonucleotide using a mutant T-7 RNA polymerase. Using nucleobase complementarity, the gemcitabine-containing RNA was annealed to an RNA aptamer that specifically targets the over-expressed EGFR receptors on pancreatic cancer cells (Nucleic Acid Therapeutics 22(5): 295-305).Oligonucleotide Synthesis:Synthesized boranophosphate-containing DNA oligonucleotides using phosphoramidite monomers with unprotected exocyclic amines. This alleviated the problem of cyclical loss of product due to the reduction of acyl protecting groups.
