PNA-NLS conjugates as single-molecular activators of target sites in double-stranded DNA for site-selective scission

Yuichiro Aiba, Yuya Hamano, Wataru Kameshima, Yasuyuki Araki, Takehiko Wada, Alessandro Accetta, Stefano Sforza, Roberto Corradini, Rosangela Marchelli, Makoto Komiyama

研究成果: Article査読

11 被引用数 (Scopus)

抄録

Artificial DNA cutters have been developed by us in our previous studies by combining two strands of pseudo-complementary peptide nucleic acid (pcPNA) with Ce(iv)-EDTA-promoted hydrolysis. The pcPNAs have two modified nucleobases (2,6-diaminopurine and 2-thiouracil) instead of conventional A and T, and can invade double-stranded DNA to activate the target site for the scission. This system has been applied to site-selective scissions of plasmid, λ-phage, E. coli genomic DNA, and human genomic DNA. Here, we have reported a still simpler and more convenient DNA cutter obtained by conjugating peptide nucleic acid (PNA) with a nuclear localization signal (NLS) peptide. This new DNA cutter requires only one PNA strand (instead of two) bearing conventional (non-pseudo-complementary) nucleobases. This PNA-NLS conjugate effectively activated the target site in double-stranded DNA and induced site-selective scission by Ce(iv)-EDTA. The complex formation between the conjugate and DNA was concretely evidenced by spectroscopic results based on time-resolved fluorescence. The target scission site of this new system was straightforwardly determined by the Watson-Crick base pairing rule, and mismatched sequences were clearly discriminated. Importantly, even highly GC-rich regions, which are difficult to be targeted by a previous strategy using pcPNA, were successfully targeted. All these features of the present DNA cutter make it promising for various future applications.

本文言語English
ページ(範囲)5233-5238
ページ数6
ジャーナルOrganic and Biomolecular Chemistry
11
32
DOI
出版ステータスPublished - 2013 8 28

ASJC Scopus subject areas

  • 生化学
  • 物理化学および理論化学
  • 有機化学

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