1. In vitro inhibition of the pim-1 protooncogene by chimeric oligodeoxyribonucleotides composed of alpha- and beta-anomeric fragments.
- Author
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Gottikh M, Baud-Demattei MV, Lescot E, Giorgi-Renault S, Shabarova Z, Dautry F, Malvy C, and Bertrand JR
- Subjects
- Animals, Base Sequence, Blood, Culture Media, Erythroblasts, Globins genetics, Humans, Hydrolysis, Mice, Molecular Sequence Data, Oligonucleotides, Antisense metabolism, Protein Biosynthesis, Proto-Oncogene Proteins antagonists & inhibitors, Proto-Oncogene Proteins c-pim-1, RNA, Messenger genetics, RNA, Messenger metabolism, Rabbits, Ribonuclease H metabolism, Oligonucleotides, Antisense pharmacology, Protein Serine-Threonine Kinases, Proto-Oncogene Proteins genetics
- Abstract
We show that oligodeoxyribonucleotides (oligos) composed of alpha- and beta-anomeric sections can be used as antisense compounds. An octamer has been chosen as an effector domain to form a substrate for RNaseH. This octamer is complementary to the translation start site of the pim-1 protooncogene mRNA. Chimeric alpha-beta oligos and their beta-analogs have a similar binding affinity for their target. These oligos also direct efficient RNaseH-mediated cleavage of target mRNA. Among all alpha-beta oligos studied, one with an alpha-fragment bound by its 3'-end to the 3'-end of the beta-octamer is the most resistant to nucleolytic digestion in biological media. The alpha-beta oligos have been found to inhibit in vitro translation of pim-1 RNA with specificity.
- Published
- 1994
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