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

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)5233-5238
Number of pages6
JournalOrganic and Biomolecular Chemistry
Volume11
Issue number32
DOIs
Publication statusPublished - 2013 Aug 28

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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