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Nucleic Acids Research, 1991, Vol. 19, No. 10 2629-2635
© 1991

MOLECULAR BIOLOGY

2'-O-methyl, 2'-O-ethyl oligoribonucleotides and phosphorothioate oligodeoxyribonucleotides as inhibitors of the in vitro U7 snRNP-dependent mRNA processing event

Matthew Cotten, Berndt Oberhauser, Helmut Brunar1, Armin Holzner1, Georg Issakides1, Christian R. Noe1, Gotthold Schaffner, Ernst Wagner and Max L. Birnstiel

Institute for Molecular Pathology Dr. Bohr Gasse 7, A-1030 Vienna, Austria 1Institut für Organische Chemie, Technische Universität Wien Getreidemarkt 9, A-1060 Vienna, Austria

Received February 26, 1991. Revised April 22, 1991. Accepted April 22, 1991.

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-modifled 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.


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