Synthese und Eigenschaften von PNA/DNA‐Chimären

Uhlmann, Eugen; Will, David W.; Breipohl, Gerhard; Langner, Dietrich; Ryte, A. S.

doi:10.1002/ange.19961082210

Cited by 12 publications

(2 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reverse DNA templates give no product in any case, because parallel binding of DNA duplexes does not occur. This latter finding is in agreement with a recent study which shows that phosphodiester/carboxamide PNA−DNA chimeras bind exclusively in the antiparallel mode to DNA . Ligation on reverse PNA templates is possible.…”

Section: Discussionsupporting

confidence: 93%

Formation of Oligonucleotide−PNA−Chimeras by Template-Directed Ligation

1998

View full text Add to dashboard Cite

DNA sequences have previously been reported to act as templates for the synthesis of PNA, and vice versa. A continuous evolutionary transition from an informational replicating system based on one polymer to a system based on the other would be facilitated if it were possible to form chimeras, that is molecules that contain monomers of both types. Here we show that ligation to form chimeras proceeds efficiently both on PNA and on DNA templates. The efficiency of ligation is primarily determined by the number of backbone bonds at the ligation site and the relative orientation of template and substrate strands. The most efficient reactions result in the formation of chimeras with ligation junctions resembling the structures of the backbones of PNA and DNA and with antiparallel alignment of both components of the chimera with the template, that is, ligations involving formation of 3'-phosphoramidate and 5'-ester bonds. However, double helices involving PNA are stable both with antiparallel and parallel orientation of the two strands. Ligation on PNA but not on DNA templates is, therefore, sometimes possible on templates with reversed orientation. The relevance of these findings to discussions of possible transitions between genetic systems is discussed.

show abstract

Section: Discussionsupporting

confidence: 93%

Formation of Oligonucleotide−PNA−Chimeras by Template-Directed Ligation

1998

View full text Add to dashboard Cite

show abstract

“…Nevertheless, progress is expected in improving PNA penetration to make feasible the in vivo use of these agents. Recently, chimeric molecules (PO/PNA) have been described as showing a good rate of cell penetration (61).…”

Section: Discussionmentioning

confidence: 99%

Modified (PNA, 2'-O-methyl and phosphoramidate) anti-TAR antisense oligonucleotides as strong and specific inhibitors of in vitro HIV-1 reverse transcription

Boulmé¹,

Freund²,

Moreau³

et al. 1998

Nucleic Acids Research

View full text Add to dashboard Cite

Natural beta-phosphodiester 16mer and 15mer antisense oligonucleotides targeted against the HIV-1 and HIV-2 TAR RNAs respectively were previously described as sequence-specific inhibitors of in vitro retroviral reverse transcription. In this work, we tested chemically modified oligonucleotide analogues: alpha-phosphodiester, phosphorothioate, methylphosphonate, peptide nucleic acid or PNA, 2'- o -methyl and (N3'-P5') phosphoramidate versions of the 16mer anti-TAR oligonucleotide. PNA, 2'- O -methyl and (N3'-P5') phosphoramidate oligomers showed a strong inhibitory effect compared with the unmodified 16mer, with reverse transcription inhibition (IC50) values in the nanomolar range. The inhibition was sequence-specific, as scrambled and mismatched control oligonucleotides were not able to inhibit cDNA synthesis. No direct binding of the 2'- O -methyl, PNA or (N3'-P5') phosphoramidate anti-TAR oligonucleotides to the HIV-1 reverse transcriptase was observed. The higher T m obtained with 2'- O -methyl, (N3'-P5') phosphoramidate and PNA molecules concerning the annealing with the stem-loop structure of the TAR RNA, in comparison with the beta-phosphodiester oligonucleotides, is correlated with their high inhibitory effect on reverse transcription.

show abstract

PNAs: synthetische Polyamidnucleinsäuren mit außergewöhnlichen Bindungseigenschaften

Uhlmann¹,

Peyman²,

Breipohl³

et al. 1998

Angewandte Chemie

Self Cite

View full text Add to dashboard Cite

Äußerst überraschend war die Erkenntnis, daß Peptidnucleinsäuren (PNAs, B=Nucleobase) trotz ihrer drastisch vom natürlichen DNA‐Rückgrat abweichenden Struktur besser als die meisten Oligonucleotidderivate als Nucleinsäuremimetica genutzt werden können. Die Synthese, physikalischen Eigenschaften und biologischen Wechselwirkungen sowohl der PNAs als auch ihrer Chimären mit DNA und RNA werden hier zusammenfassend beschrieben.

show abstract

Synthese und Eigenschaften von PNA/DNA‐Chimären

Cited by 12 publications

References 23 publications

Formation of Oligonucleotide−PNA−Chimeras by Template-Directed Ligation

Formation of Oligonucleotide−PNA−Chimeras by Template-Directed Ligation

Modified (PNA, 2'-O-methyl and phosphoramidate) anti-TAR antisense oligonucleotides as strong and specific inhibitors of in vitro HIV-1 reverse transcription

PNAs: synthetische Polyamidnucleinsäuren mit außergewöhnlichen Bindungseigenschaften

Contact Info

Product

Resources

About