Structure of a human telomeric DNA sequence stabilized by 8-bromoguanosine substitutions, as determined by NMR in a K+ solution

FEBS J. 2007 Jul;274(14):3545-3556. doi: 10.1111/j.1742-4658.2007.05881.x. Epub 2007 Jun 11.


The structure of human telomeric DNA is controversial; it depends upon the sequence contexts and the methodologies used to determine it. The solution structure in the presence of K(+) is particularly interesting, but the structure is yet to be elucidated, due to possible conformational heterogeneity. Here, a unique strategy is applied to stabilize one such structure in a K(+) solution by substituting guanosines with 8-bromoguanosines at proper positions. The resulting spectra are cleaner and led to determination of the structure at a high atomic resolution. This demonstrates that the application of 8-bromoguanosine is a powerful tool to overcome the difficulty of nucleic acid structure determination arising from conformational heterogeneity. The obtained structure is a mixed-parallel/antiparallel quadruplex. The structure of telomeric DNA was recently reported in another study, in which stabilization was brought about by mutation and resultant additional interactions [Luu KN, Phan AT, Kuryavyi V, Lacroix L & Patel DJ (2006) Structure of the human telomere in K(+) solution: an intramolecular (3+1) G-quadruplex scaffold. J Am Chem Soc 128, 9963-9970]. The structure of the guanine tracts was similar between the two. However, a difference was seen for loops connecting guanine tracts, which may play a role in the higher order arrangement of telomeres. Our structure can be utilized to design a small molecule which stabilizes the quadruplex. This type of molecule is supposed to inhibit a telomerase and thus is expected to be a candidate anticancer drug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cations / chemistry
  • DNA / chemistry*
  • DNA / genetics*
  • Guanine / chemistry
  • Guanosine / analogs & derivatives*
  • Guanosine / chemistry
  • Humans
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Nucleic Acid Conformation* / drug effects
  • Potassium / chemistry*
  • Potassium / pharmacology
  • Solutions
  • Telomere / genetics*


  • Cations
  • Solutions
  • Guanosine
  • 8-bromoguanosine
  • Guanine
  • DNA
  • Potassium