title: Modulation of ras expression by anti-sense, nonionic deoxyoligonucleotide analogs.
abstract: 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.
authors.affiliation: Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.
authors.forename: D
authors.initials: D
authors.lastname: Brown
authors.forename: Z P
authors.initials: ZP
authors.lastname: Yu
authors.forename: P
authors.initials: P
authors.lastname: Miller
authors.forename: K
authors.initials: K
authors.lastname: Blake
authors.forename: C
authors.initials: C
authors.lastname: Wei
authors.forename: H F
authors.initials: HF
authors.lastname: Kung
authors.forename: R J
authors.initials: RJ
authors.lastname: Black
authors.forename: P O
authors.initials: PO
authors.lastname: Ts'o
authors.forename: E H
authors.initials: EH
authors.lastname: Chang
mesh_terms: 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
chemical_list: D003062:Codon; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; C021992:dideoxyribonucleoside methylphosphonates