The Institute of Scientific and Industrial Research, Osaka University, Ibaraki 567-0047, Japan.
Bioorg Med Chem Lett. 2012 Mar 1;22(5):2000-3. doi: 10.1016/j.bmcl.2012.01.030. Epub 2012 Jan 25.
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.
三核苷酸重复的异常扩张已被确定为遗传性神经退行性疾病的常见机制。尽管重复扩展的实际机制仍不确定，但三核苷酸重复的不稳定性可能与在重复序列中形成的替代 DNA 发夹结构的稳定性增加有关。在这里，我们报告了一种合成配体萘啶基氨基甲酸二聚体（NCD）选择性地结合并稳定 CGG 重复序列中的内链发夹结构。NCD-CGG 发夹复合物是一种稳定的结构，可有效干扰 Taq DNA 聚合酶的 DNA 复制。考虑到 NCD 的序列偏好，NCD 的使用对于研究人类基因组中 CGG/CCG 重复序列的遗传不稳定性将是有价值的。
