A small molecule that disrupts G-quadruplex DNA structure and enhances gene expression

Waller, Zoë A. E., Sewitz, Sven A., Hsu, Shang-Te Danny and Balasubramanian, Shankar (2009) A small molecule that disrupts G-quadruplex DNA structure and enhances gene expression. Journal of the American Chemical Society, 131 (35). pp. 12628-12633.

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It has been hypothesized that the formation of G-quadruplex structures in the DNA of gene promoters may be functionally linked to transcription and consequently that small molecules that interact with such G-quadruplexes may modulate transcription. We previously reported that triarylpyridines are a class of small molecules that selectively interact with G-quadruplex DNA. Here we describe an unexpected property of one such ligand that was found to disrupt the structure of two different DNA G-quadruplex structures, each derived from sequence motifs in the promoter of the proto-oncogene c-kit. Furthermore, cell-based experiments in a cell line that expresses c-kit (HGC-27) showed that the same ligand increased the expression of c-kit. This contrasts with G-quadruplex-inducing ligands that have been previously found to inhibit gene expression. It would thus appear that the functional consequence of small molecule ligands interacting with G-quadruplex structures may depend on the specific mode of interaction. These observations provide further evidence to suggest that G-quadruplex forming sequence motifs play a role that relates to transcription.

Item Type: Article
Faculty \ School: Faculty of Science > School of Pharmacy
UEA Research Groups: Faculty of Science > Research Groups > Chemical Biology and Medicinal Chemistry (former - to 2021)
Faculty of Science > Research Groups > Medicinal Chemistry (former - to 2017)
Depositing User: Rachel Smith
Date Deposited: 17 Mar 2011 14:33
Last Modified: 27 Jul 2023 07:20
URI: https://ueaeprints.uea.ac.uk/id/eprint/26565
DOI: 10.1021/ja901892u

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