2'-O-methyl, 2'-O-ethyl oligoribonucleotides and phosphorothioate oligodeoxyribonucleotides as inhibitors of the in vitro U7 snRNP-dependent mRNA processing event.
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.
Cotten
M
M
Institute for Molecular Pathology, Vienna, Austria.
Oberhauser
B
B
Brunar
H
H
Holzner
A
A
Issakides
G
G
Noe
C R
CR
Schaffner
G
G
Wagner
E
E
Birnstiel
M L
ML
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*
D006657:Histones; D009838:Oligodeoxyribonucleotides; D009843:Oligoribonucleotides; D016372:RNA, Antisense; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D013873:Thionucleotides; D012313:RNA