Europe PMC funders group europe PMC funders author manuscripts a small molecule that disrupts g-quadruplex DNA structure and enhances gene expression. Waller, Z. A E, Sewitz, S. A, & Hsu, S. D. Journal of The American Chemical Society, 131(35):12628–12633, 2009. 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 = {Europe {PMC} funders group europe {PMC} funders author manuscripts a small molecule that disrupts g-quadruplex {DNA} structure and enhances gene expression},
volume = {131},
issn = {1520-5126},
doi = {10.1021/ja901892u.A},
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 and Sewitz, Sven A and Hsu, Shang-te Danny},
year = {2009},
pmid = {19689109},
keywords = {\#nosource, ⚠️ Invalid DOI},
pages = {12628--12633},
}
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