Nuclease resistance and RNase H sensitivity of oligonucleotides bridged by oligomethylenediol and oligoethylene glycol linkers

Antisense & Nucleic Acid Drug Development
P E VorobjevH Seliger

Abstract

The properties of new chimeric oligodeoxynucleotides made of short sequences (tetramers, pentamers, octamers, and decamers) bridged by hexamethylenediol and hexaethylene glycol linkers have been investigated. These chimeric oligonucleotides showed an improved resistance toward snake venom 3'-phosphodiesterase, with an increased stability when a terminal 3'-3'-internucleotide phosphodiester bond is present. It also has been demonstrated that the hybrid complexes formed by bridged oligonucleotides and a complementary 20-mer RNA are able to elicit the activity of ribonuclease H (RNase H) from Escherichia coli. The substrate properties of chimeric oligonucleotides depend on the length of the oligonucleotide fragments bridged by linkers. Introduction of a nonnucleotide spacer into the native oligonucleotide only slightly hampers the extent of the RNA hydrolysis in the hybrid complexes, whereas a modification of the site of reaction is observed as a possible consequence of the steric disturbance due to the aliphatic linkers. Hence, these new chimeric oligonucleotides, namely, short oligonucleotide fragments bridged by nonnucleotide linkers, demonstrate a favorable combination of exonuclease resistance and high substrate activity towa...Continue Reading

References

Sep 11, 1979·Nucleic Acids Research·H Donis-Keller
Aug 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·T M WoolfC G Jennings
Feb 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·S AgrawalT Pederson
Apr 25, 1988·Nucleic Acids Research·C A SteinJ S Cohen

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Citations

Nov 1, 2003·Bioorganic & Medicinal Chemistry Letters·Masaharu MurataYoshiki Katayama
Feb 24, 2006·Journal of Biomolecular Structure & Dynamics·D V PyshnyiE M Ivanova
Dec 2, 2014·The Journal of Physical Chemistry. B·Vu H LeEdwin A Lewis
Nov 25, 2004·Nucleosides, Nucleotides & Nucleic Acids·Inna A PyshnayaEugenia M Ivanova
Mar 22, 2007·Bioconjugate Chemistry·Bénédicte M PâtureauMasad J Damha

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