Biomedical subjects

Luciano Mayol

Publications and source records attributed to Luciano Mayol.

25 records · Page 2Linked to original sources

PubMed2004

Effects of an 8-bromodeoxyguanosine incorporation on the parallel quadruplex structure [d(TGGGT)]4.

NMR, molecular dynamics and mechanics calculations, and CD spectroscopy were used to characterise three tetramolecular quadruplex complexes: [d(TG(Br)GGT)](4), [d(TGG(Br)GT)](4) and [d(TGGG(Br)T)](4), where G(Br) indicates an 8-bromoguanine residue. All three quadruplexes are characterised by a 4-fold symmetry with all strands parallel to each other and, differently to what has been observed for other parallel quadruplex structures, with a tetrad (formed by 8-Br-dGs) in a syn conformation. The whole of the data demonstrates that the replacement in turn of different dG residues with 8-Br-dG in the sequence 5[prime or minute]-TGGGT-3[prime or minute] affects the resulting structures in different ways, leading to different CD profiles and thermal stabilities. Particularly, [d(TG(Br)GGT)](4) and [d(TGG(Br)GT)](4) are more stable than the unmodified sequence, whereas [d(TGGG(Br)T)](4) is much less stable than the natural counterpart. The conformational features found in the three quadruplexes might, in principle, amplify the range of applicability of synthetic oligonucleotides as aptamers or catalysts, by providing novel structural motifs with different molecular recognition capabilities from those of native DNA sequences.

Base Sequence↗

PubMed2003

Effect of a modified thymine on the structure and stability of [d(TGGGT)]4 quadruplex.

Telomeric guanine-rich sequence can adopt quadruplex structures that are important for their biological role in chromosomal stabilisation. G quartets are characterised by the cyclic hydrogen bonding of four guanine bases in a coplanar arrangement and their stability is ion-dependent. In this work we compare the stability of [d(TGGGT)](4) and [d(T*GGGT)](4) quadruplexes. The last one contains a modified thymine, where the hydroxyl group substitutes one hydrogen atom of the methyl group of the thymine in the [d(TGGGT)](4) sequence. We used a combination of spectroscopic, calorimetric and computational techniques to characterise the G-quadruplex formation. NMR and CD spectra of [d(T*GGGT)](4) were characteristic of parallel-stranded, tetramolecular quadruplex. CD and DSC melting experiments reveal that [d(T*GGGT)](4) is less stable that unmodified quadruplex. Molecular models suggest possible explanation for the observed behaviour.

Calorimetry, Differential Scanning↗

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↗

PubMedDate not supplied

1H-NMR study of the quadruplex [d(TGGGT)]4 containing a modified thymine.

A NMR structural study of quadruplex [d(TGGGT)]4 containing a modified thymine is reported. The three dimensional structure of the complex is very similar to those of other parallel stranded quadruplexes. The modified thymines (T*) are able, at least in the minimised structures, to form a tetrad containing extra H-bonds through the hydroxyl groups. Nevertheless, in this new tetrad the modified thymines are slightly open towards the solvent respect to the unmodified T-tetrad.

Base Sequence↗

PubMedDate not supplied

PNA-DNA chimeras forming quadruplex structures.

1H-NMR, CD, and UV spectroscopy have been used to investigate the structure of PNA/DNA chimeras forming quadruplex structures. In particular, we synthesized 5'TGGG3'-t (1) and 5'TGG3'-gt (2), where lower and upper case letters indicate PNA and DNA residues, respectively. CD spectrum and all NMR data of (1) are typical of quadruplexes involving four parallel strands. UV melting profile of (1) indicates that its thermal stability is quite similar to that observed for the reference structure [d(TGGGT)]4. 1H-NMR spectrum for 5'TGG3'-gt (2) shows that this oligonucleotide is not able to fold into a single, well-defined species.

Base Sequence↗