Specific interactions with intra- and intermolecular G-quadruplex DNA structures by hydrosoluble coronene derivatives: A new class of telomerase inhibitors

Study of binding affinity and selectivity of perylene and coronene derivatives towards duplex and quadruplex DNA by ESI‐MS

“…The data collected show that all the tested molecules are good G-quadruplex binders, able to bind quadruplex DNA either with 1 : 1 or 2 : 1 stoichiometries. This agrees with the general model of interactions between G-quadruplex DNA and quadruplex ligands: ligand molecules stack on the terminal G-tetrad [7,24,25] (Fig. 3).…”

“…[13,18,30] Other than this simple G-quadruplex model, we selected two oligonucleotides whose sequences are very similar to human telomeric DNA: TSG4 and F21TTT, whose sequences are (5 -GGGATTGGGATTGGGATTGGGTT-3 ) and (5 -GGGTTAGGGTTAGGGTTAGGGTT-3 ) respectively. The first oligo, having an inverted loop with respect to human telomeric repeats, has been widely used in polyacrylamide gel electrophoresis (PAGE) and telomeric repeat amplification protocol (TRAP) tests on Gquadruplex ligands, being a suitable substrate for telomerase elongation in vitro, [24,25,27,31] while F21TTT presents the correct sequence of the loops, similar to the oligonucleotide used in the fluorescence resonance energy transfer (FRET) assay [32] and characterized by X-ray crystallography in K + solution. [33] Both oligos are 23 nucleotides long, a dimension comparable to that of the oligonucleotides used in several other ESI-MS studies, [17,18,30,34] and are supposed to fold in a monomeric Gquadruplex structure.…”

“…[17,18] We have selected for the ESI-MS analysis one perylene diimide carrying as a bay-substituent a tertiary amine [PIP-PIPER(1,7)], [22] two four-chained perylene diimides carrying as a bay-substituents a secondary and tertiary amine [DAPER4C (1,7) and DAPER4C(1,6)], [23] one three-chained perylene derivative (DAPER3C) [25] and one coronene derivative (CORON). [24] The simple, not bay-substituted perylene diimide PIPER [26,27,29,35,36] has also been tested to make a comparison between our synthesized molecules and this deeply studied perylene compound (Scheme 1). In fact, all the analyzed molecules present a greater number of polar side chains and/or a larger aromatic core with respect to PIPER.…”

“…Comparing K 1 and K 2 values, we can assume that no cooperativity is involved in the binding 6)] and a monomeric G-quadruplex (cyan surface) obtained by simulated annealing. [24,33] The ligand is in yellow as sticks (top) and as atom type colored sticks and yellow surfaces (bottom, under a different perspective). Guanines are shown as red sticks and the surface of interaction with the ligand in light blue.…”

1,3-Dien-5-ynes: Versatile Building Blocks for the Synthesis of Carbo- and Heterocycles

“…78 Although high yields are usually obtained in these reactions, quite harsh conditions are required. The base-mediated cycloaromatization has been applied to the synthesis of the alkaloid tylophorine, 79 coronene derivatives acting as telomerase inhibitors, 80 angular-shaped anthradiselenophenes 81 and naphthodithiophenes 82 with promising optoelectronic applications, thienoacenes 53 and ethene-bridged terthiophenes. 83 …”