Structure of an unprecedented G-quadruplex scaffold in the human c-kit promoter

J Am Chem Soc. 2007 Apr 11;129(14):4386-92. doi: 10.1021/ja068739h. Epub 2007 Mar 16.


The c-kit oncogene is an important target in the treatment of gastrointestinal tumors. A potential approach to inhibition of the expression of this gene involves selective stabilization of G-quadruplex structures that may be induced to form in the c-kit promoter region. Here we report on the structure of an unprecedented intramolecular G-quadruplex formed by a G-rich sequence in the c-kit promoter in K+ solution. The structure represents a new folding topology with several unique features. Most strikingly, an isolated guanine is involved in G-tetrad core formation, despite the presence of four three-guanine tracts. There are four loops: two single-residue double-chain-reversal loops, a two-residue loop, and a five-residue stem-loop, which contain base-pairing alignments. This unique structural scaffold provides a highly specific platform for the future design of ligands specifically targeted to the promoter DNA of c-kit.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / chemistry*
  • DNA / genetics
  • G-Quadruplexes
  • Humans
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Nucleic Acid Conformation*
  • Promoter Regions, Genetic* / genetics
  • Proto-Oncogene Proteins c-kit / genetics*
  • Solutions


  • Solutions
  • DNA
  • Proto-Oncogene Proteins c-kit