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. 1994 Dec 20;91(26):12433–12437. doi: 10.1073/pnas.91.26.12433

Triple-strand-forming methylphosphonate oligodeoxynucleotides targeted to mRNA efficiently block protein synthesis.

M A Reynolds 1, L J Arnold Jr 1, M T Almazan 1, T A Beck 1, R I Hogrefe 1, M D Metzler 1, S R Stoughton 1, B Y Tseng 1, T L Trapane 1, P O Ts'o 1, et al.
PMCID: PMC45452  PMID: 7528921

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.

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Selected References

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