Member PUBLICATIONS

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• Thermodynamic analysis of quadruplex DNA-drug interaction.

  Publication Date: 01/01/2007 on Nucleosides, nucleotides & nucleic acids

  by Pagano B, Mattia CA, Virno A, Randazzo A, Mayol L, Giancola C

  DOI: 10.1080/15257770701499069

  This work studies the binding properties of distamycin and its carbamoyl analog, containing four pyrrole units, with the [d(TGGGGT)](4) quadruplex by means of isothermal titration calorimetry (ITC). Analysis of the ITC data reveals that drug/quadruplex binding stoichiometry is 1:1 for both interactions and that distamycin analog gives approximately a 10-fold increase in the quadruplex affinity.

• Structural insight into the hTERT intron 6 sequence d(GGGGTGAAAGGGG) from 1H-NMR study.

  Publication Date: 01/01/2007 on Nucleosides, nucleotides & nucleic acids

  by Virno A, Mayol L, Ramos A, Fraternali F, Pagano B, Randazzo A

  DOI: 10.1080/15257770701521854

  The interest in DNA quadruplex structures has been fueled by the recognition that telomeres, the 3' single stranded guanine-rich overhangs found at the termini of chromosomes, are likely to form G-tetrads type structures important in cell senescence and cancer. In addition to their presence in telomeres, where they may play a role in maintaining the stability and integrity of chromosomes, guanine-rich regions are found in other region of the genome, amongst these is intron 6 of hTERT a gene codifying for the enzyme telomerase. Interestingly, the formation of G-quadruplexes in this region is involved in the down-regulation of telomerase activity caused by an alteration of the hTERT splicing pattern. Therefore, we have analyzed several sequences of that intron by (1)H-NMR and CD spectroscopy, and we have found that the sequence d(GGGGTGAAAGGGG) is able to fold in a single well-defined antiparallel quadruplex structure consisting of four G-tetrads, possessing a twofold symmetry, and containing four Gs in a syn glycosidic conformation.

• Thermodynamics and kinetics of PNA-DNA quadruplex-forming chimeras.

  Publication Date: 23/11/2005 on Journal of the American Chemical Society

  by Petraccone L, Pagano B, Esposito V, Randazzo A, Piccialli G, Barone G, Mattia CA, Giancola C

  DOI: 10.1021/ja0545923

  PNA-DNA chimeras present the interesting properties of PNA, such as the high binding affinity to complementary single-strand (DNA or RNA), and the resistance to nuclease and protease degradation. At the same time, the limitations of an oligomer containing all PNA residues, such as low water solubility, self-aggregation, and low cellular uptake, are effectively overcome. Further, PNA-DNA chimeras possess interesting biological properties as antisense agents. We have explored the ability of PNA-DNA chimeric strands to assemble in quadruplex structures. The rate constant for association of the quadruplexes and their thermodynamic properties have been determined by CD spectroscopy and differential scanning calorimetry (DSC). Thermal denaturation experiments indicated higher thermal and thermodynamic stabilities for chimeric quadruplexes in comparison with the corresponding unmodified DNA quadruplex. Singular value decomposition analysis (SVD) suggests the presence of kinetically stable intermediate species in the quadruplex formation process. The experimental results have been discussed on the basis of molecular dynamic simulations. The ability of PNA-DNA chimeras to form stable quadruplex structures expands their potential utility as therapeutic agents.

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