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

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.

SUBMITTER: Phan AT

PROVIDER: S-EPMC4693632 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature

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

Phan Anh Tuân AT Kuryavyi Vitaly V Burge Sarah S Neidle Stephen S Patel Dinshaw J DJ

Journal of the American Chemical Society 20070316 14

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 ...[more]

PMID: 17362008

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