Synthesis of azide congeners of <scp> preQ ₁ </scp> as potential substrates for <scp>tRNA</scp> guanine transglycosylase

PreQ1 (2) is a precursor of queuine (1) that in eubacteria incorporated into transfer RNA (tRNA) by tRNA guanine transglycosylase (TGT) before being further elaborated queuine. The modification unusual and occurs across all eukaryotes with few exceptions, but its function remains unclear. As the modified nucleotide through incorporation specially synthesized instead via genetically encoded base, study sites prepared probes possible. We report synthesis two novel azide congeners (3,4) preQ1 for this purpose. evaluation their interaction TGT shows both act as weak competitive inhibitors exchange guanine(34) tRNATyr Ki ~70 μM. However, we could not show these are substrates TGT-catalyzed tRNA. believe reason marked loss binding due to functionality 3 4 abrogating possibility hydrogen bonds carbonyl group Leu231 Met260 TGT, previously observed terminal methylene amine x-ray crystallography.