期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 131, 期 35, 页码 12628-12633出版社
AMER CHEMICAL SOC
DOI: 10.1021/ja901892u
关键词
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资金
- BBSRC
- Cancer Research UK
- Human Frontier Long-Term Fellowship [LT0798/2005]
- National Science Council of the Republic of China, Taiwan [NSC97-2917-1-564-102]
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.
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