論文

査読有り
2016年5月

Deciphering the genomic targets of alkylating polyamide conjugates using high-throughput sequencing

NUCLEIC ACIDS RESEARCH
  • Anandhakumar Chandran
  • ,
  • Junetha Syed
  • ,
  • Rhys D. Taylor
  • ,
  • Gengo Kashiwazaki
  • ,
  • Shinsuke Sato
  • ,
  • Kaori Hashiya
  • ,
  • Toshikazu Bando
  • ,
  • Hiroshi Sugiyama

44
9
開始ページ
4014
終了ページ
4024
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1093/nar/gkw283
出版者・発行元
OXFORD UNIV PRESS

Chemically engineered small molecules targeting specific genomic sequences play an important role in drug development research. Pyrrole-imidazole polyamides (PIPs) are a group of molecules that can bind to the DNA minor-groove and can be engineered to target specific sequences. Their biological effects rely primarily on their selective DNA binding. However, the binding mechanism of PIPs at the chromatinized genome level is poorly understood. Herein, we report a method using high-throughput sequencing to identify the DNA-alkylating sites of PIP-indole-seco-CBI conjugates. High-throughput sequencing analysis of conjugate 2 showed highly similar DNA-alkylating sites on synthetic oligos (histone-free DNA) and on human genomes (chromatinized DNA context). To our knowledge, this is the first report identifying alkylation sites across genomic DNA by alkylating PIP conjugates using high-throughput sequencing.

リンク情報
DOI
https://doi.org/10.1093/nar/gkw283
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/27098039
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000377472100015&DestApp=WOS_CPL
ID情報
  • DOI : 10.1093/nar/gkw283
  • ISSN : 0305-1048
  • eISSN : 1362-4962
  • PubMed ID : 27098039
  • Web of Science ID : WOS:000377472100015

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