Synthesis and characterization of a mini-library of new conjugated d(TGGGAG) oligonucleotides with potential anti-HIV activity.

In the search for ODNs endowed with relevant antiviral properties, Hotoda and coworkers investigated a series of G-quadruplex-forming ODNs, finally focusing on modified d(TGGGAG) ODNs conjugated with aromatic residues at the 5-end. These were found to exhibit potent anti-HIV activity associated with low cytotoxicity when carrying at the 5′-end bulky aromatic residues. Recently we described a general approach to obtain a mini library of new d(TGGGAG) ODNs, conjugated with different aromatic groups at the 5’-end through a phosphodiester bond. Several modified sequences showed pronounced anti-HIV-1 activity and they showed high binding affinities for the HIV-1 envelope gp120 and gp41. In these structures the 5-end residues play a major role on the G-quadruplex stability, dramatically enhancing stability of the quadruplex complexes (Tm>20°C). With the final goal to expand the repertoire of accessible end-modified G-rich ODNs, and to get a more complete picture of their structure-activity relationships, we describe herein the synthesis and characterization of a mini-library of new d(5’TGGGAG3’) carrying hydrophobic groups at the 5’-end and 2-hydroxyethylphosphate group at the 3'-end, connected through phosphodiester and phosphoramidate bonds, respectively. In order to study the influence of the conjugation at the ends of the oligonucleotide chains on their ability to form quadruplex structures, a CD analysis was undertaken on the conjugated oligomers in comparison with the corresponding unmodified d(TGGGAG) oligomer

Harpin oligonucleotides forming G-quadruplexes: new aptamers with potential anti-HIV activity

Several G-rich synthetic oligodeoxyribonucleotides (ODNs) have shown promising biological properties, ranging from anticancer to anti-HIV activities. G-quadruplex formation was found to be a crucial prerequisite in determining these biological effects. Aptamers exhibiting anti-HIV activity represent an important class of potential therapeutics. Recently we described the synthesis and characterization of new d(TGGGAG) ODNs, conjugated with different aromatic groups at the 5’-end through a phosphodiester bond. The modified sequences showed a parallel stranded tetramolecular G-quadruplexes CD profile and a pronounced anti-HIV-1 activity. Herein, with the aim to use d(TGGGAG) as a lead sequence for a more effective anti-HIV agent, we propose the fully automated synthesis of new ODNs containing two d(TGGGAG) sequences whose 3-ends are joint by an hexaethylenglycole loop. CD analysis was undertaken on the 3’-3’ linked d(TGGGAG) hairpins in comparison with the corresponding unmodified oligomers. Besides, in order to study the influence of the conjugation at the ends of the harpin chains on their ability to stabilize quadruplex structures and on their anti-HIV activity, different conjugated oligomers have been studied

Sull'opportunità della determinazione della prolattinemia nelle candidate all'assunzione di estroprogestinici

[no abstract available