Triple-strand-forming methylphosphonate oligodeoxynucleotides targeted to mRNA efficiently block protein synthesis.
Open Access
- 20 December 1994
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 91 (26) , 12433-12437
- https://doi.org/10.1073/pnas.91.26.12433
Abstract
Antisense oligonucleotides are ordinarily targeted to mRNA by double-stranded (Watson-Crick) base recognition but are seldom targeted by triple-stranded recognition. We report that certain all-purine methylphosphonate oligodeoxyribonucleotides (MPOs) form stable triple-stranded complexes with complementary (all-pyrimidine) RNA targets. Modified chloramphenicol acetyltransferase mRNA targets were prepared with complementary all-pyrimidine inserts (18-20 bp) located immediately 3' of the initiation codon. These modified chloramphenicol acetyltransferase mRNAs were used together with internal control (nontarget) mRNAs in a cell-free translation-arrest assay. Our data show that triple-strand-forming MPOs specifically inhibit protein synthesis in a concentration-dependent manner (> 90% at 1 microM). In addition, these MPOs specifically block reverse transcription in the region of their complementary polypyrimidine target sites.Keywords
This publication has 18 references indexed in Scilit:
- Current concepts in antisense drug designJournal of Medicinal Chemistry, 1993
- The binding of an antisense oligonucleotide to a hairpin structure via triplex formation inhibits chemical and biological reactionsNucleic Acids Research, 1993
- An Improved Method for the Synthesis and Deprotection of Methylphosphonate OligonucleotidesPublished by Springer Nature ,1992
- Stabilities of double- and triple-strand helical nucleic acidsProgress in Biophysics and Molecular Biology, 1992
- Structure and Applications of Intermolecular DNA TriplexesThe Lancet Healthy Longevity, 1992
- DNA triple‐helix formation: An approach to artificial gene repressors?BioEssays, 1992
- Antisense inhibition of ras p21 expression that is sensitive to a point mutationBiochemistry, 1991
- Comparative circular dichroism and fluorescence studies of oligodeoxyribonucleotide and oligodeoxyribonucleoside methylphosphonate pyrimidine strands in duplex and triplex formationBiochemistry, 1991
- Specific regulation of gene expression by antisense, sense and antigene nucleic acidsBiochimica et Biophysica Acta (BBA) - Gene Structure and Expression, 1990
- Role of RNase H in hybrid-arrested translation by antisense oligonucleotides.Proceedings of the National Academy of Sciences, 1988