TRIPLE-STRAND-FORMING METHYLPHOSPHONATE OLIGODEOXYNUCLEOTIDES TARGETED TO MESSENGER-RNA EFFICIENTLY BLOCK PROTEIN-SYNTHESIS

Citation
Ma. Reynolds et al., TRIPLE-STRAND-FORMING METHYLPHOSPHONATE OLIGODEOXYNUCLEOTIDES TARGETED TO MESSENGER-RNA EFFICIENTLY BLOCK PROTEIN-SYNTHESIS, Proceedings of the National Academy of Sciences of the United Statesof America, 91(26), 1994, pp. 12433-12437
Citations number
24
Categorie Soggetti
Multidisciplinary Sciences
ISSN journal
00278424
Volume
91
Issue
26
Year of publication
1994
Pages
12433 - 12437
Database
ISI
SICI code
0027-8424(1994)91:26<12433:TMOT>2.0.ZU;2-I
Abstract
Antisense oligonucleotides are ordinarily targeted to mRNA by double-s tranded (Watson-Crick) base recognition but are seldom targeted by tri ple-stranded recognition. We report that certain all-purine methylphos phonate oligodeoxyribonucleotides (MPOs) form stable triple-stranded c omplexes with complementary (all-pyrimidine) RNA targets. Modified chl oramphenicol acetyltransferase mRNA targets were prepared with complem entary all-pyrimidine inserts (18-20 bp) located immediately 3' of the initiation codon. These modified chloramphenicol acetyltransferase mR NAs were used together with internal control (nontarget) mRNAs in a ce ll-free translation-arrest assay. Our data show that triple-strand-for ming MPOs specifically inhibit protein synthesis in a concentration-de pendent manner (> 90% at 1 mu M). In addition, these MPOs specifically block reverse transcription in the region of their complementary poly pyrimidine target sites.