G-quadruplexes (GQs) are non-canonical DNA structures composed of stacks of stabilized G-tetrads. GQs are firmly established as biologically viable targets for the development of anticancer therapeutics. Nine variants of a telomeric GQ from the organism <i>T. thermophile</i> (TET), with the repeat (TTGGGG)n, were studied alone and in complex with the highly selective GQ ligand, N-methylmesoporphyin IX (NMM). Biophysical characterization concluded that most TET sequences fold into GQs but only two of them (Tel14 and TET4B) are homogeneous. All GQs adopt a hybrid conformation with the exception of Tel14A (parallel) and TET4B (predominantly antiparallel). Moreover, all TET sequences are stable above room temperature. Biophysical studies have also concluded that the addition of NMM converts all the sequences to a parallel conformation as well as increases their stability by 7-12 °C. Excitingly, diffraction quality crystals of TET4B and Tel26 were grown. The best data set for TET4B has a resolution of 1.97 Å and data reproducibility (Rmeas) of 4.8%.

Studying and solving the structures of G-quadruplex telomeric sequences from <i>T. thermophile</i>

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

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Studying and solving the structures of G-quadruplex telomeric sequences from T. thermophile