作者
Anh Tuân Phan, Vitaly Kuryavyi, Sarah Burge, Stephen Neidle, Dinshaw J Patel
发表日期
2007/4/11
期刊
Journal of the American Chemical Society
卷号
129
期号
14
页码范围
4386-4392
出版商
American Chemical Society
简介
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.
引用总数
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学术搜索中的文章
AT Phan, V Kuryavyi, S Burge, S Neidle, DJ Patel - Journal of the American Chemical Society, 2007