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

Authors
Journal
Bioorganic & Medicinal Chemistry
0968-0896
Publisher
Elsevier
Publication Date
Volume
3
Issue
4
Identifiers
DOI: 10.1016/0968-0896(95)00033-d
Disciplines
  • Biology

Abstract

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.

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