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  • Title: Stable triple helices formed by oligonucleotide N3'-->P5' phosphoramidates inhibit transcription elongation.
    Author: Escudé C, Giovannangeli C, Sun JS, Lloyd DH, Chen JK, Gryaznov SM, Garestier T, Hélène C.
    Journal: Proc Natl Acad Sci U S A; 1996 Apr 30; 93(9):4365-9. PubMed ID: 8633072.
    Abstract:
    Oligonucleotide analogs with N3'-->P5' phosphoramidate linkages bind to the major groove of double-helical DNA at specific oligopurine.oligopyrimidine sequences. These triple-helical complexes are much more stable than those formed by oligonucleotides with natural phosphodiester linkages. Oligonucleotide phosphoramidates containing thymine and cytosine or thymine, cytosine, and guanine bind strongly to the polypurine tract of human immunodeficiency virus proviral DNA under physiological conditions. Site-specific cleavage by the Dra I restriction enzyme at the 5' end of the polypurine sequence was inhibited by triplex formation. A eukaryotic transcription assay was used to investigate the effect of oligophosphoramidate binding to the polypurine tract sequence on transcription of the type 1 human immunodeficiency virus nef gene under the control of a cytomegalovirus promoter. An efficient arrest of RNA polymerase II was observed at the specific triplex site at submicromolar concentrations.
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