A small molecule that disrupts G-quadruplex DNA structure and enhances gene expression. Waller, Z. a E Z. A E, Sewitz, S. A, Hsu, S. D., & Balasubramanian, S. Journal of the American Chemical Society, 131(35):12628–33, September, 2009. tex.ids= wallerSmallMoleculeThat2009![A small molecule that disrupts G-quadruplex DNA structure and enhances gene expression. [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex 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.
@article{Waller2009,
title = {A small molecule that disrupts {G}-quadruplex {DNA} structure and enhances gene expression.},
volume = {131},
issn = {1520-5126},
url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3037543&tool=pmcentrez&rendertype=abstract http://dx.doi.org/10.1021/ja901892u},
doi = {10.1021/ja901892u},
abstract = {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.},
number = {35},
journal = {Journal of the American Chemical Society},
author = {Waller, Zoë a E Zoë A E and Sewitz, Sven A and Hsu, Shang-Te Danny and Balasubramanian, Shankar},
month = sep,
year = {2009},
pmid = {19689109},
note = {tex.ids= wallerSmallMoleculeThat2009},
keywords = {\#nosource, Absorption, Animals, Base Sequence, Cell Line, Circular Dichroism, DNA, DNA: chemistry, DNA: genetics, G-Quadruplexes, G-Quadruplexes: drug effects, Genetic, Genetic: drug effects, Humans, Magnetic Resonance Spectroscopy, Proto-Oncogene Proteins c-kit, Proto-Oncogene Proteins c-kit: genetics, Pyridines, Pyridines: chemistry, Pyridines: pharmacology, Spectrophotometry, Transcription, Ultraviolet},
pages = {12628--33},
}
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