Nucleic Acids Research, Vol 24, Issue 18 3522-3526, Copyright © 1996 by Oxford University Press
J Hall, D Husken and R Haner
Lanthanide complexes covalently attached to oligonucleotides have been
shown to cleave RNA in a sequence-specific manner. Efficient cleavage,
however, is at present limited to single-stranded RNA regions, as RNA in a
duplex is considerably more resistant to strand scission. To overcome this
limitation, we have designed and synthesised artificial nucleases
comprising lanthanide complexes covalently linked to
oligodeoxyribonucleotides which cleave a partially complementary RNA at a
bulged site, in the duplex region. Strand scission occurs at or near the
bulge. Cleavage of the RNA target by the metal complex can be addressed via
the major or the minor groove. In an example of a competitive situation,
where the cleavage moiety has access to both a bulge and a single-strand
region, transesterification at the bulge is favoured. Such artificial
ribonucleases may find application as antisense agents and as tools in
molecular biology. In addition, the results may have importance for the
design of artificial ribonucleases which are able to act with catalytic
turnover.
ARTICLES
Towards artificial ribonucleases: the sequence-specific cleavage of RNA in a duplex
Central Research Laboratories, Ciba, Basel, Switzerland.
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