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

Eur J Med Chem. 2015 Jan 7:89:51-8. doi: 10.1016/j.ejmech.2014.10.030. Epub 2014 Oct 14.

Abstract

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.

Keywords: Anti-HIV activity; Aptamers; Conjugated hairpin oligonucleotides; G-quadruplexes; Solid-phase synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Aptamers, Nucleotide / chemical synthesis
  • Aptamers, Nucleotide / chemistry
  • Aptamers, Nucleotide / pharmacology*
  • G-Quadruplexes*
  • HIV-1 / drug effects*
  • HIV-2 / drug effects*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Oligonucleotides / chemical synthesis
  • Oligonucleotides / chemistry
  • Oligonucleotides / pharmacology*
  • Surface Plasmon Resonance

Substances

  • Anti-HIV Agents
  • Aptamers, Nucleotide
  • Oligonucleotides