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

Phan, A.T., Kuryavyi, V., Burge, S., Neidle, S. and Patel, D.J. (2007) Structure of an unprecedented G-quadruplex scaffold in the human c-kit promoter. Journal of the American Chemical Society, 129 (14). pp. 4386-4392. 10.1021/ja068739h.

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DOI: 10.1021/ja068739h


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.

Item Type:Article
Additional Information:Full text available in print and electronically from the School of Pharmacy Library.
Departments, units and centres:Department of Pharmaceutical and Biological Chemistry > Cancer Research UK Biomolecular Structure Group
ID Code:1758
Journal or Publication Title:Journal of the American Chemical Society
Deposited By:Library Staff
Deposited On:13 Aug 2010 11:54
Last Modified:20 Jan 2012 17:48

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