2',5'-linked oligo-3'-deoxyribonucleoside phosphorothioate chimeras: thermal stability and antisense inhibition of gene expression.
2',5'-Linked oligo-3'-deoxyribonucleotides bind selectively to complementary RNA but not to DNA. These oligonucleotides (ODNs) do not recognize double-stranded DNA by Hoogsteen triplex formation and the complexes formed by these ODNs with RNA are not substrates for Escherichia coli RNase H. Substitution of the 2',5'-phosphodiester backbone by phosphorothioate linkages gives 2',5'-linked oligo-3'-deoxynucleoside phosphorothioate ODNs that exhibit significantly less non-specific binding to cellular proteins or thrombin. Incorporation of a stretch of seven contiguous 3',5'-linked oligo-2'-deoxynucleoside phosphorothioate linkages in the center of 2',5'-linked ODNs (as a putative RNase H recognition site) afford chimeric antisense ODNs that retain the ability to inhibit steroid 5alpha-reductase (5alphaR) expression in cell culture.
Bhan
P
P
Dyad Pharmaceutical Corporation, 9110 Red Branch Road, Columbia, MD 21045, USA. purshotam.bhan@am.pharmacia.com
Bhan
A
A
Hong
M
M
Hartwell
J G
JG
Saunders
J M
JM
Hoke
G D
GD
D001482:Base Composition; D004268:DNA-Binding Proteins / Q000737:chemistry; D004722:Endoribonucleases / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology; D005786:Gene Expression Regulation; D009691:Nucleic Acid Denaturation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D016914:Ribonuclease H / Q000378:metabolism; D013329:Structure-Activity Relationship; D013873:Thionucleotides / Q000737:chemistry*
D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; D016914:Ribonuclease H