Characterization of the nuclear binding sites of oligodeoxyribonucleotides and their analogs.
The intracellular fate of antisense oligodeoxyribonucleotide (oligomers) is poorly understood. Recent observations strongly suggest that after endocytosis and escape from the endocytic compartments, oligomers accumulate in the nuclei of eukaryotic cells by simple diffusion. Isolated nuclei were used to determine the number of these nuclear binding sites and their affinity for phosphodiester, phosphorothioate, and methyl-phosphonate oligomers. These cell-free assays were correlated with intact cell microinjection experiments. Great differences have been observed between these analogs. These data are helpful in understanding the fate of oligomers and the mechanism of their action and could be helpful for a more rational design of antisense molecules.
Clarenc
J P
JP
Centre Nationale de la Recherche Scientifique UA1191, Université de Montpellier II Sciences et Techniques du Languedoc, France.
Lebleu
B
B
Léonetti
J P
JP
D001483:Base Sequence; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism*; D002474:Cell-Free System; D005456:Fluorescent Dyes; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008845:Microinjections; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000378:metabolism*
D005456:Fluorescent Dyes; D009838:Oligodeoxyribonucleotides