Modulation of ras expression by anti-sense, nonionic deoxyoligonucleotide analogs.
Anti-ras oligodeoxyribonucleoside methylphosphonates (ONMP's) complementary to the initiation codon region have been synthesized to explore their efficacy and specificity on ras-p21 translation. ONMP (IC-0) precisely complementing the first initial 11 nucleotides of the Balb-ras initiation codon region acts in a dose-dependent manner to inhibit p21 translation by a rabbit reticulocyte lysate. At 100 microM, IC-0 inhibits the cell-free translation of p21 close to completion. The two control oligomers containing one or two nucleotide mismatches were significantly less effective than IC-0 at the equivalent concentration. In living cells, a perfectly matched ONMP directed against the initiation codon region inhibited Ha-ras p21 expression by 90% at a concentration of 50 microM.
Brown
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D
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.
Yu
Z P
ZP
Miller
P
P
Blake
K
K
Wei
C
C
Kung
H F
HF
Black
R J
RJ
Ts'o
P O
PO
Chang
E H
EH
D000818:Animals; D003062:Codon; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D011905:Genes, ras; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D009841:Oligonucleotides / Q000235:genetics*; D016376:Oligonucleotides, Antisense; D010957:Plasmids; D011233:Precipitin Tests; D014176:Protein Biosynthesis; D011817:Rabbits; D014158:Transcription, Genetic
D003062:Codon; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; C021992:dideoxyribonucleoside methylphosphonates