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

Abstract We describe the facile syntheses of new modified oligonucleotides based on d(TG 3 AG) 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(TG 3 AG) sequence.