Stacking of G-quadruplexes: NMR structure of a G-rich oligonucleotide with potential anti-HIV and anticancer activity

Nucleic Acids Res. 2011 Nov;39(21):9448-57. doi: 10.1093/nar/gkr539. Epub 2011 Aug 12.

Abstract

G-rich oligonucleotides T30695 (or T30923), with the sequence of (GGGT)(4), and T40214, with the sequence of (GGGC)(4), have been reported to exhibit anti-HIV and anticancer activity. Here we report on the structure of a dimeric G-quadruplex adopted by a derivative of these sequences in K(+) solution. It comprises two identical propeller-type parallel-stranded G-quadruplex subunits each containing three G-tetrad layers that are stacked via the 5'-5' interface. We demonstrated control over the stacking of the two monomeric subunits by sequence modifications. Our analysis of possible structures at the stacking interface provides a general principle for stacking of G-quadruplexes, which could have implications for the assembly and recognition of higher-order G-quadruplex structures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • G-Quadruplexes*
  • Guanine / chemistry
  • HIV Integrase / metabolism
  • HIV Integrase Inhibitors / chemistry*
  • HIV Integrase Inhibitors / pharmacology
  • Inosine / chemistry
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Oligonucleotides / chemistry*
  • Oligonucleotides / pharmacology
  • Potassium / chemistry

Substances

  • Antineoplastic Agents
  • HIV Integrase Inhibitors
  • Oligonucleotides
  • Inosine
  • Guanine
  • HIV Integrase
  • Potassium
  • p31 integrase protein, Human immunodeficiency virus 1