RMSd conformation of C3 and A1T3 mutated G-quadruplex sequences.

<p>Lowest (A) and highest (B) RMSd conformation of C3 and A1T3 mutated G-quadruplex sequences during 2 ns MD simulations with respect to the starting structure (2HY9). The DNA is shown in purple (C3) and aquamarine (A1T3) wireframe rendering and its strand as orange cartoon. The K⁺ coordinating ions are represented as blue spheres. The RMSd value of each conformation is reported and expressed in Å. </p

CD spectra of telomeric oligonucleotides mutated in the loop.

<p>A) Each oligonucleotide contained one single base mutated to C in each loop; B) each oligonucleotide contained the three nucleotides mutated to C in one loop; C) A bases in the loops were moved from the third to the second and first positions or mutated to T.</p

CD spectra of telomeric oligonucleotides mutated in the loop.

<p>In each oligonucleotide one single base was mutated. </p

Thermal difference spectra (TDS) and TDS factor plots of three representative oligonucleotides.

<p>A) TDS of C1, C2 and C3 sequences; B) TDS factors of C1, C2 and C3 sequences. TDS and TDS factors of all oligonucleotides are available in Figure S8 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084113#pone.0084113.s004" target="_blank">File S4</a>.</p

Frequency of the occurrence of the hydrogen bonds.

<p>Frequency of the occurrence of the hydrogen bonds (HBs), monitored over 2 ns, every 10 ps, in the guanine core in the presence of C3 and A1T3 mutated G-quadruplex sequences. </p

Model structures of conformations reported for the human telomeric sequence.

<p>Guanosines in dark grey are <i>syn</i>, and those in light gray are <i>anti</i>.</p

Clerocidin protection assay of the wt, C1, C2 and C3 telomeric oligonucleotides.

<p>Sequences were heat denatured, folded in the presence or absence of K⁺ and treated with CL followed by hot piperidine (CL lanes) or just treated with piperidine (C lanes). M indicates the marker lane obtained with the Maxam and Gilbert protocol. Base sequences are shown aside each gel image. Symbols * and ~ indicate protected G and C bases, respectively.</p

CD-monitored thermal denaturing assays of wt, C1, C2 and C3 telomeric oligonucleotides.

<p>A-D) CD spectra of each indicated oligonucleotide measured at increasing temperatures (20°C-95°). Arrows indicate curve trend at increasing temperatures. E) Molar ellipticities, measured at wavelength of maximum intensity, were plotted against temperature.</p

Identification and Characterization of New DNA G‑Quadruplex Binders Selected by a Combination of Ligand and Structure-Based Virtual Screening Approaches

Nowadays, it has been demonstrated that DNA G-quadruplex arrangements are involved in cellular aging and cancer, thus boosting the discovery of selective binders for these DNA secondary structures. By taking advantage of available structural and biological information on these structures, we performed a high throughput in silico screening of commercially available molecules databases by merging ligand- and structure-based approaches by means of docking experiments. Compounds selected by the virtual screening procedure were then tested for their ability to interact with the human telomeric G-quadruplex folding by circular dichroism, fluorescence spectroscopy, and photodynamic techniques. Interestingly, our screening succeeded in retrieving a new promising scaffold for G-quadruplex binders characterized by a psoralen moiety

Kaempferol as Selective Human MAO‑A Inhibitor: Analytical Detection in Calabrian Red Wines, Biological and Molecular Modeling Studies

The purpose of this work was to determine the kaempferol content in three red wines of Calabria, a southern Italian region with a great number of certified food products. Considering that wine cultivar, climate, and soil influence the qualitative and quantitative composition in flavonoids of Vitis vinifera L. berries, the three analyzed samples were taken from the 2013 vintage. Moreover, the Gaglioppo samples, with assigned Controlled Origin Denomination (DOC), were also investigated in the production of years 2008, 2010, and 2011. In addition to the analysis of kaempferol, which is present in higher concentration than in other Italian wines, in vitro assays were performed to evaluate, for the first time, the inhibition of the human monoamine oxidases (hMAO-A and hMAO-B). Molecular recognition studies were also carried out to provide insight into the binding mode of kaempferol and selectivity of inhibition of the hMAO-A isoform