Journal Article

Chiral and steric effects in the efficient binding of α-anomeric deoxyoligonucleoside N-alkylphosphoramidates to ssDNA and RNA

Alain Laurent, Magali Naval, Françoise Debart, Jean-Jacques Vasseur and Bernard Rayner

in Nucleic Acids Research

Volume 27, issue 21, pages 4151-4159
Published in print November 1999 | ISSN: 0305-1048
Published online November 1999 | e-ISSN: 1362-4962 | DOI: https://dx.doi.org/10.1093/nar/27.21.4151
Chiral and steric effects in the efficient binding of α-anomeric deoxyoligonucleoside N-alkylphosphoramidates to ssDNA and RNA

More Like This

Show all results sharing these subjects:

  • Chemistry
  • Biochemistry
  • Bioinformatics and Computational Biology
  • Genetics and Genomics
  • Molecular and Cell Biology

GO

Show Summary Details

Preview

We report hybridization properties of new phosphate-modified α-oligonucleoside analogs with non-ionic or cationic internucleotide linkages such as methoxy-ethylphosphoramidate (PNHME), phosphoromorpholi-date (PMOR) and dimethylaminopropylphosphor-amidate (PNHDMAP). First we evaluated the chirality effect of the phosphorus atom on the affinity of α- or β-dodecanucleoside phosphodiesters containing one chirally enriched N-alkylphosphoramidate linkage located in the middle of the sequence d(TCTT-AA*CCCACA). As for P-substituted β-oligonucleo-tides, a difference in binding behavior between the two diastereoisomers (difference in ΔTm) exists in the hybridization properties of α-analogs when DNA was the target but this effect was not detrimental to duplex stability. This effect was considerably reduced when RNA was the target. Secondly we studied the effect of steric hindrance around phosphorus on the affinity of fully modified β- and α-oligo-nucleoside N-alkylphosphoramidates for their DNA and RNA targets. This effect was very weak with α-analogs whereas it was more pronounced with β-oligos. PNHME-modified α-oligonucleosides formed more stable duplexes with DNA (ΔTm +9.6°C) and RNA (ΔTm +1.4°C) targets than the ‘parent’ phosphodiester. Finally, base pairing specificity of these α-oligonucleo-side N-alkylphosphoramidates for their targets was found to be as high as for natural oligonucleoside phosphodiesters.

Journal Article.  4771 words.  Illustrated.

Subjects: Chemistry ; Biochemistry ; Bioinformatics and Computational Biology ; Genetics and Genomics ; Molecular and Cell Biology

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content. subscribe or login to access all content.