title: 2'-O-methyl, 2'-O-ethyl oligoribonucleotides and phosphorothioate oligodeoxyribonucleotides as inhibitors of the in vitro U7 snRNP-dependent mRNA processing event.
abstract: We describe the synthesis of 2'-O-methyl, 2'-O-ethyl oligoribonucleotides and phosphorothioate oligodeoxyribonucleotides and demonstrate their utility as inhibitors of the in vitro U7 snRNP-dependent mRNA processing event. These 2'-O-modified compounds were designed to possess the binding affinity of an RNA molecule towards a complementary RNA target with an enhanced stability against nucleases. The 2'-O-methyl and 2'-O-ethyl antisense compounds function as potent inhibitors of the reaction at 1-10 nM, approximately 5-fold more effective than a natural antisense RNA molecule and requiring an approximate 5-fold excess over the target RNA for 80% inhibition of the processing reaction.
authors.affiliation: Institute for Molecular Pathology, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Cotten
authors.forename: B
authors.initials: B
authors.lastname: Oberhauser
authors.forename: H
authors.initials: H
authors.lastname: Brunar
authors.forename: A
authors.initials: A
authors.lastname: Holzner
authors.forename: G
authors.initials: G
authors.lastname: Issakides
authors.forename: C R
authors.initials: CR
authors.lastname: Noe
authors.forename: G
authors.initials: G
authors.lastname: Schaffner
authors.forename: E
authors.initials: E
authors.lastname: Wagner
authors.forename: M L
authors.initials: ML
authors.lastname: Birnstiel
mesh_terms: D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D006657:Histones / Q000096:biosynthesis; D008745:Methylation; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000494:pharmacology*; D009843:Oligoribonucleotides / Q000737:chemistry / Q000494:pharmacology*; D012313:RNA; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects*; D016372:RNA, Antisense; D012261:Ribonucleoproteins / Q000187:drug effects / Q000502:physiology*; D017411:Ribonucleoproteins, Small Nuclear; D013873:Thionucleotides / Q000494:pharmacology*
chemical_list: D006657:Histones; D009838:Oligodeoxyribonucleotides; D009843:Oligoribonucleotides; D016372:RNA, Antisense; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D013873:Thionucleotides; D012313:RNA