Hairpin oligonucleotides forming G-quadruplexes: New aptamers with anti-HIV activity

• A new hairpin ODN quadruplex-based anti-HIV was reported.
• These oligomers all possessed high thermal stability.
• These oligomers showed anti-HIV activity at low μM concentrations.
• These oligomers all possessed elevated resistance in human serum.

We describe the facile syntheses of new modified oligonucleotides based on d(TG3AG) that form bimolecular G-quadruplexes and possess a HEG loop as an inversion of polarity site 3′-3′ or 5′-5′ and aromatic residues conjugated to the 5′-end through phosphodiester bonds. The conjugated hairpin G-quadruplexes exhibited parallel orientation, high thermal stability, elevated resistance in human serum and high or moderate anti-HIV-1 activity with low cytotoxicity. Further, these molecules showed significant binding to HIV envelope glycoproteins gp120, gp41 and HSA, as revealed by SPR assays. As a result, these conjugated hairpins represent the first active anti-HIV-1 bimolecular G-quadruplexes based on the d(TG3AG) sequence.

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