In vitro inhibition of the pim-1 protooncogene by chimeric oligodeoxyribonucleotides composed of alpha- and beta-anomeric fragments.
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.
Laboratoire de Biochimie-Enzymologie, CNRS URA 147, Institut Gustave Roussy, Villejuif, France.
M
M
Gottikh
M V
MV
Baud-Demattei
E
E
Lescot
S
S
Giorgi-Renault
Z
Z
Shabarova
F
F
Dautry
C
C
Malvy
J R
JR
Bertrand
D000818:Animals; D001483:Base Sequence; D001769:Blood; D003470:Culture Media; D004900:Erythroblasts; D005914:Globins / Q000235:genetics; D006801:Humans; D006868:Hydrolysis; D051379:Mice; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000378:metabolism / Q000494:pharmacology*; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D051573:Proto-Oncogene Proteins c-pim-1; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D016914:Ribonuclease H / Q000378:metabolism
D003470:Culture Media; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D005914:Globins; C496634:PIM1 protein, human; C496636:Pim1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1; D016914:Ribonuclease H