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In this work, we report the solution structure, thermodynamic studies, and the pharmacological properties of a new modified thrombin binding aptamer (TBA) containing a G-LNA residue, namely d(5'-GGTTGGTGTGGTTGg-3'), where upper case and lower case letters represent DNA and LNA residues, respectively. NMR and CD spectroscopy, as well as molecular dynamics(More)
The complex between distamycin A and the parallel DNA quadruplex [d(TGGGGT)]4 has been studied by 1H NMR spectroscopy and isothermal titration calorimetry (ITC). To unambiguously assert that distamycin A interacts with the grooves of the quadruplex [d(TGGGGT)]4, we have analyzed the NMR titration profile of a modified quadruplex, namely [d(TGGMeGGT)]4, and(More)
In the past decade, DNA G-quadruplexes have come into the limelight thanks to their biological implications and to their potential druggability in anticancer therapy. In particular, it has been found that small molecules that stabilize G-quadruplex structures are effective inhibitors of telomerase which plays a critical role in tumorigenesis. So far, the(More)
A physico-chemical characterization, based on NMR and CD spectroscopy, of quadruplexes formed by the oligonucleotide d(TGGGT), where two or three Gs are substituted by 8-bromo-2'-deoxyguanosine residues (dGBr), is reported. The oligonucleotidic sequences d(TGBr GBr GT), d(TGBr GGBr T), d(TGGBr GBr T), and d(TGBr GBr GBr T) have been synthesized. Only(More)
Differential scanning calorimetry (DSC) and circular dichroism (CD) techniques were used to investigate the physico-chemical properties of the quadruplexes formed by the two different truncations of human telomeric sequence d(TAGGGT) and d(AGGGT), where the adenines were substituted by 2'-deoxy-8-(hydroxyl)adenosine (A --> A OH). CD spectra show that the(More)
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(More)
The use of small molecules that bind and stabilize G-quadruplex structures is emerging as a promising way to inhibit telomerase activity in tumor cells. In this paper, isothermal titration calorimetry (ITC) and 1H NMR studies have been conducted to examine the binding of distamycin A and its two carbamoyl derivatives (compounds 1 and 2) to the target(More)
The study of DNA G-quadruplex stabilizers has enjoyed a great momentum in the late years due to their application as anticancer agents. The recognition of the grooves of these structural motifs is expected to result in a higher degree of selectivity over other DNA structures. Therefore, to achieve an enhanced knowledge on the structural and conformational(More)
The solution structure of a new modified thrombin binding aptamer (TBA) containing a 5'-5' inversion of polarity site, namely d(3'GGT5'-5'TGGTGTGGTTGG3'), is reported. NMR and CD spectroscopy, as well as molecular dynamic and mechanic calculations, have been used to characterize the 3D structure. The modified oligonucleotide is characterized by a chair-like(More)
Structural insight into DNA quadruplex structures formed by oligodeoxyribonucleotides 3'TG5'-5'GGGT3' (QS55) and 5'TG3'-3'GGGT5' (QS33) is presented. NMR analysis reveals that QS33 forms a parallel-like four-fold symmetric quadruplex, while QS55 possesses a two-fold symmetry and is characterized by a tetrameric antiparallel quadruplex embedded between two(More)