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

Zoë A. E. Waller, Sven A. Sewitz, Shang-Te Danny Hsu, Shankar Balasubramanian

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121 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)12628-12633
Number of pages6
JournalJournal of the American Chemical Society
Issue number35
Publication statusPublished - 18 Aug 2009

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