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Michela Varra

Publications and source records attributed to Michela Varra.

11 recordsLinked to original sources
PubMed2006

Synthesis and characterization of DNA quadruplexes containing T-tetrads formed by bunch-oligonucleotides.

The solid phase syntheses of the bunch oligonucleotides and based on the sequences of the natural oligodeoxynucleotides (ODNs) d(TG2TG2C) and d(CG2TG2T), respectively, attached to a non-nucleotidic tetrabranched linker, are reported. Bunch-ODNs and were shown to form more stable monomolecular parallel G-quadruplexes and when compared with their tetramolecular counterparts [d(TG2TG2C)]4 and [d(CG2TG2T)]4, respectively. The structure and stability of all the synthesized complexes have been investigated by circular dichroism (CD), CD thermal denaturation experiments, and 1H-NMR (nuclear magnetic resonance) experiments at variable temperatures. Particularly, the spectroscopic data confirmed that 1 adopts a T-tetrad containing parallel-stranded quadruplex structure as in the tetramolecular complex.

Circular Dichroism↗
PubMed2005

Unusual monomolecular DNA quadruplex structures using bunch-oligonucleotides.

The chemical synthesis of several G-rich bunch-oligonucleotides and the structural characterization of the corresponding monomolecular G-quadruplexes (I-IV) have been reported. The synthetic method allow the achievement of monomolecular DNA quadruplex structures having unusual and predeterminable oligodeoxyribonucleotide (ODN) strand orientation.

DNA↗
PubMed2004

Effect of gamma-hydroxypropano deoxyguanosine, the major acrolein-derived adduct, on monomolecular quadruplex structure of telomeric repeat d(TTAGGG)(4).

The three oligodeoxyribonucleotides (ODNs) a-c, having the telomeric repeat d(TTAGGG)(4) sequence and incorporating gamma-hydroxypropano deoxyguanosine at different positions, were synthesized. Gel electrophoresis and CD analyses indicated that the ODNs assume monomolecular quadruplex structures in Na+ and in K+ buffers. The T(m) values, obtained by CD melting experiments, showed that the presence of the acrolein-dG adduct into the ODN b decreases the thermal stability of the monomolecular quadruplex structure in Na+ solution, whereas for a and c no significant effect could be detected in the same experimental conditions. On the contrary, all ODNs a-d show the same behaviour in K+ buffer. These findings are briefly discussed.

Acrolein↗
PubMed2004

Structural study of four-stranded quadruplex structures containing 2'-deoxy-8-(propyn-1-yl)adenosine.

In this paper, we report the NMR structural study of two quadruplex structures formed by truncations of the human telomeric sequence and containing a modified base, namely d(AprGGGT) and d(TAprGGGT), where Apr indicates 2'-deoxy-8-(propyn-1-yl)adenosines. Both oligonucleotides have been found to form 4-fold symmetric G-quadruplex structures with all strands parallel and equivalent to each other and characterized by higher thermal stabilities than the natural counterparts. The presence of the propynyl groups affects the conformations of the 5' edge of both quadruplexes in such a way to prevent the formation of one of the two possible H-bond patterns observed for a canonical A-tetrad. The increased thermal stabilities of the modified quadruplexes seem to be mostly due to a prevalent syn glycosidic conformation assumed by the Apr residues.

Base Sequence↗
PubMed2002

Interaction of distamycin A and netropsin with quadruplex and duplex structures: a comparative 1H-NMR study.

Homonuclear NMR techniques have been used to investigate the interactions of the minor groove binding agents distamycin A (Dist-A) and the related drug netropsin (Net) with three quadruplexes characterized by different groove widths: [d(TGGGGT)]4 (Q1), [d(GGGGTTTTGGGG)]2 (Q2), and d(GGGGTTGGGGTGTGGGGTTGGGG) (Q3). Netropsin has been found to be in a fast chemical exchange with all three kinds of quadruplexes, whereas Dist-A interacts tightly with Q1 and, at a less extent, with Q2. In order to determine the degree of selectivity of Dist-A for two- rather than four-stranded DNA, we titrated with Dist-A an equimolar solution of Ql and the duplex d(CGCAAATTTGCG)2 (D). This comparative 1H-NMR study allowed us to conclude that Dist-A and, consequently, Net possess higher affinity for duplex DNA.

Base Composition↗
PubMedDate not supplied

Synthesis and characterization of monomolecular DNA G-quadruplexes formed by tetra-end-linked oligonucleotides.

Guanine-rich DNA sequences are widely dispersed in the eukaryotic genome and are abundant in regions with relevant biological significance. They can form quadruplex structures stabilized by guanine quartets. These structures differ for number and strand polarity, loop composition, and conformation. We report here the syntheses and the structural studies of a set of interconnected d(TG(4)T) fragments which are tethered, with different orientations, to a tetra-end-linker in an attempt to force the formation of specific four-stranded DNA quadruplex structures. Two synthetic strategies have been used to obtain oligodeoxyribonucleotide (ODN) strands linked with their 3'- or 5'-ends to each of the four arms of the linker. The first approach allowed the synthesis of tetra-end-linked ODN (TEL-ODN) containing the four ODN strands with a parallel orientation, while the latter synthetic pathway led to the synthesis of TEL-ODNs each containing antiparallel ODN pairs. The influence of the linker at 3'- or 5'-ODN, on the quadruplex typology and stability, in the presence of sodium or potassium ions, has been investigated by circular dichroism (CD), CD thermal denaturation, (1)H NMR experiments at variable temperature, and molecular modeling. All synthesized TEL-ODNs formed parallel G-quadruplex structures. Particularly, the TEL-ODN containing all parallel ODN tracts formed very stable parallel G-quadruplex complexes, whereas the TEL-ODNs containing antiparallel ODN pairs led to relatively less stable parallel G-quadruplexes. The molecular modeling data suggested that the above antiparallel TEL-ODNs can adopt parallel G-quadruplex structures thanks to a considerable folding of the tetra-end-linker around the whole quadruplex scaffold.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Oligonucleotides containing an acridine group covalently bonded to the nucleotide flanking the 3'-3' phosphodiester junction for alternate strand triple helix formation.

Oligonucleotides with a 3'-3' inversion of polarity and containing an acridine group attached to nucleotide base flanking the 3'-3' phosphodiester bon have been synthesized, characterized and used as third strand in alternate triple helix formation. CD melting studies and molecular mechanics calculations have been carried out to investigate these triplex structures.

Acridines↗