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Lookup NU author(s): Professor Olaf Heidenreich
Oligonucleotide N3'-->P5'phosphoramidates are a new and promising class of antisense agents. Here we report biological properties of phosphoramidate oligonucleotides targeted against the human T cell leukemia virus type-I Tax protein, the major transcriptional transactivator of this human retrovirus. Isosequential phosphorothioate oligodeoxynucleotides and uniformly modified and chimeric phosphoramidate oligodeoxynucleotides containing six central phosphodiester linkages are all quite stable in cell nuclei. The uniformly modified anti-tax phosphoramidate oligodeoxynucleotide does not activate nuclear RNase H, as was shown by RNase protection assay. In contrast, the chimeric phosphoramidate-phosphodiester oligodeoxynucleotide is an efficient activator of RNase H. The presence of one or two mismatched nucleotides in the phosphodiester portion of oligonucleotides affected this activation only negligibly. When introduced into tax-transformed fibroblasts ex vivo, only the uniformly modified anti-tax phosphoramidate oligodeoxynucleotide caused a sequence-dependent reduction in the Tax protein level. Neither the chimeric phosphoramidate nor the phosphorothioate oligodeoxynucleotides significantly reduced tax expression under similar experimental conditions.
Author(s): Heidenreich O, Gryaznov S, Nerenberg M
Publication type: Article
Publication status: Published
Journal: Nucleic Acids Research
Year: 1997
Volume: 25
Issue: 4
Pages: 776-780
Date deposited: 17/02/2012
ISSN (print): 0305-1048
ISSN (electronic): 1362-4954
URL: http://dx.doi.org/10.1093/nar/25.4.776
DOI: 10.1093/nar/25.4.776
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