Format

Send to

Choose Destination
J Am Chem Soc. 2007 Apr 11;129(14):4386-92. Epub 2007 Mar 16.

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

Author information

1
Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. phantuan@ntu.edu.sg

Abstract

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.

PMID:
17362008
PMCID:
PMC4693632
DOI:
10.1021/ja068739h
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Chemical Society Icon for PubMed Central
Loading ...
Support Center