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.