title: 2',5'-linked oligo-3'-deoxyribonucleoside phosphorothioate chimeras: thermal stability and antisense inhibition of gene expression.
abstract: 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.
authors.affiliation: Dyad Pharmaceutical Corporation, 9110 Red Branch Road, Columbia, MD 21045, USA. purshotam.bhan@am.pharmacia.com
authors.forename: P
authors.initials: P
authors.lastname: Bhan
authors.forename: A
authors.initials: A
authors.lastname: Bhan
authors.forename: M
authors.initials: M
authors.lastname: Hong
authors.forename: J G
authors.initials: JG
authors.lastname: Hartwell
authors.forename: J M
authors.initials: JM
authors.lastname: Saunders
authors.forename: G D
authors.initials: GD
authors.lastname: Hoke
mesh_terms: 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*
chemical_list: D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; D016914:Ribonuclease H