Use of trifluoromethylated nucleotide analogs as 19F‐NMR probes of DNA structure

Abstract

The dynamics of conformational changes in DNA and RNA are important in many biological processes. Fluorine NMR has been shown to be a valuable structural tool for studying RNA and DNA and their interactions with other compounds. Unfortunately, many of the fluorinated nucleosides utilized are either unstable, expensive, or change nucleic acid structure. We report our efforts toward the synthesis of the phosphoramidites of 8‐aza‐7‐deaza‐7‐trifluoromethyl guanosine, 8‐aza‐7‐deaza‐7‐trifluoromethyl adenosine, 8‐trifluoromethyl guanosine and 8‐trifluoromethyl adenosine ribonucleosides. We also report our efforts in incorporating the analogs into DNA, the impact of the analogs on DNA stability using thermal denaturation, and our initial NMR experimental results.