Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 127, Issue 30, Pages 10584-10589Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja050823u
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Funding
- Cancer Research UK [A5709] Funding Source: Medline
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The DNA sequence, d(AGGGAGGGCGCTGGGAGGAGGG), occurs within the promoter region of the c-kit oncogene. We show here, using a combination of NMR, circular dichroism, and melting temperature measurements, that this sequence forms a four-stranded quadruplex structure under physiological conditions. Variations in the sequences that intervene between the guanine tracts have been examined, and surprisingly, none of these modified sequences forms a quadruplex arrangement under these conditions. This suggests that the occurrence of quadruplex-forming sequences within the human and other genomes is less than was hitherto expected. The c-kit quadruplex may be a new target for therapeutic intervention in cancers where there is elevated expression of the c-kit gene.
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