Targeting peptide nucleic acid-protein conjugates to structural features within duplex DNA

James C. Norton, John H. Waggenspack, Elana Varnum, David R. Corey

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

A convenient small scale synthesis has been developed for obtaining peptide nucleic acid oligomers (PNAs). PNAs have been conjugated to a protein, staphylococcal nuclease, through disulfide exchange between a cysteine at the 3′-(carboxy) end of the PNA and an introduced cysteine on the surface of the nuclease. Site specific DNA cleavage by the attached nuclease has been used to examine the Watson-Crick hybridization of the PNAs to duplex DNA. Substantial affinity cleavage occurred when target sites contained inverted repeats which have the potential to form non B-DNA structures such as cruciforms. No affinity cleavage was observed at a site lacking apparent potential for non B-DNA structures. These results indicate that the Watson-Crick hybridization of PNAs to duplex DNA by strand displacement is favored by the presence of potential alternative secondary structures within the target sequence.

Original languageEnglish (US)
Pages (from-to)437-445
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume3
Issue number4
DOIs
StatePublished - Apr 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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