論文

査読有り 国際誌
2020年2月6日

New Modified Deoxythymine with Dibranched Tetraethylene Glycol Stabilizes G-Quadruplex Structures.

Molecules (Basel, Switzerland)
  • Hisae Tateishi-Karimata
  • ,
  • Tatsuya Ohyama
  • ,
  • Takahiro Muraoka
  • ,
  • Shigenori Tanaka
  • ,
  • Kazushi Kinbara
  • ,
  • Naoki Sugimoto

25
3
記述言語
英語
掲載種別
DOI
10.3390/molecules25030705

Methods for stabilizing G-quadruplex formation is a promising therapeutic approach for cancer treatment and other biomedical applications because stable G-quadruplexes efficiently inhibit biological reactions. Oligo and polyethylene glycols are promising biocompatible compounds, and we have shown that linear oligoethylene glycols can stabilize G-quadruplexes. Here, we developed a new modified deoxythymine with dibranched or tribranched tetraethylene glycol (TEG) and incorporated these TEG-modified deoxythymines into a loop region that forms an antiparallel G-quadruplex. We analyzed the stability of the modified G-quadruplexes, and the results showed that the tribranched TEG destabilized G-quadruplexes through entropic contributions, likely through steric hindrance. Interestingly, the dibranched TEG modification increased G-quadruplex stability relative to the unmodified DNA structures due to favorable enthalpic contributions. Molecular dynamics calculations suggested that dibranched TEG interacts with the G-quadruplex through hydrogen bonding and CH-π interactions. Moreover, these branched TEG-modified deoxythymine protected the DNA oligonucleotides from degradation by various nucleases in human serum. By taking advantage of the unique interactions between DNA and branched TEG, advanced DNA materials can be developed that affect the regulation of DNA structure.

リンク情報
DOI
https://doi.org/10.3390/molecules25030705
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32041318
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036917
ID情報
  • DOI : 10.3390/molecules25030705
  • PubMed ID : 32041318
  • PubMed Central 記事ID : PMC7036917

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