Structure of an Unprecedented G-Quadruplex Scaffold in the Human c-kit Promoter

Structure of an Unprecedented G-Quadruplex Scaffold in the Human c-kit Promoter. Phan, A. T., Kuryavyi, V., Burge, S., Neidle, S., & Patel, D. J. Journal of the American Chemical Society, 129(14):4386–4392, April, 2007.

Paper doi abstract bibtex

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.

@article{phan_structure_2007,
	title = {Structure of an {Unprecedented} {G}-{Quadruplex} {Scaffold} in the {Human} \textit{c-kit} {Promoter}},
	volume = {129},
	issn = {0002-7863, 1520-5126},
	url = {https://pubs.acs.org/doi/10.1021/ja068739h},
	doi = {10.1021/ja068739h},
	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.},
	language = {en},
	number = {14},
	urldate = {2020-11-09},
	journal = {Journal of the American Chemical Society},
	author = {Phan, Anh Tuân and Kuryavyi, Vitaly and Burge, Sarah and Neidle, Stephen and Patel, Dinshaw J.},
	month = apr,
	year = {2007},
	pages = {4386--4392},
}

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