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

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 th...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Bioorganic & medicinal chemistry 1995-04, Vol.3 (4), p.437-445
Hauptverfasser: Norton, James C., Waggenspack, John H., Varnum, Elana, Corey, David R.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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. A convenient small scale PNA synthesis strategy has been developed and used to afford PNAs for attachment to staphylococcal nuclease. Affinity cleavage reveals conjugates hybridize at inverted repeats within ds DNA
ISSN:0968-0896
1464-3391
DOI:10.1016/0968-0896(95)00033-D