Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 22, Issue 5, Pages 2000-2003Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2012.01.030
Keywords
(CGG)(n) repeats; DNA replication; Small molecules; DNA recognition
Categories
Funding
- Human Frontier Science Program [HFSP RGY79/2007]
- National Science Fund of China [21002024]
- Grants-in-Aid for Scientific Research [23241073] Funding Source: KAKEN
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Unusual expansion of trinucleotide repeats has been identified as a common mechanism of hereditary neurodegenerative diseases. Although the actual mechanism of repeat expansion remains uncertain, trinucleotide repeat instability may be related to the increased stability of an alternative DNA hairpin structure formed in the repeat sequences. Here we report that a synthetic ligand naphthyridine carbamate dimer (NCD) selectively bound to and stabilized an intra-stranded hairpin structure in CGG repeat sequences. The NCD-CGG hairpin complex was a stable structure that efficiently interfered with DNA replication by Taq DNA polymerase. Considering the sequence preference of NCD, the use of NCD would be valuable to investigate the genetic instabilities of CGG/CCG repeat sequences in human genomes. (C) 2012 Elsevier Ltd. All rights reserved.
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