5´-O-Methylphosphonate nucleic acids—new modified DNAs that increase the Escherichia coli RNase H cleavage rate of hybrid duplexes

0428075 - ÚFE 2015 RIV GB eng J - Journal Article
Šípová, Hana - Špringer, Tomáš - Rejman, Dominik - Šimák, Ondřej - Petrová, Magdalena - Novák, Pavel - Rosenbergová, Šárka - Páv, Ondřej - Liboska, Radek - Barvík, I. - Štěpánek, J. - Rosenberg, Ivan - Homola, Jiří
5´-O-Methylphosphonate nucleic acids—new modified DNAs that increase the Escherichia coli RNase H cleavage rate of hybrid duplexes.
Nucleic Acids Research. Roč. 42, č. 8 (2014), s. 5378-5389. ISSN 0305-1048. E-ISSN 1362-4962
R&D Projects: GA ČR GA203/09/0820; GA ČR GA13-26526S
Institutional support: RVO:67985882 ; RVO:61388963
Keywords : Antisense Oligonucleotides * Ribonuclease H * Surface Plasmon Resonance
Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering; CC - Organic Chemistry (UOCHB-X)
Impact factor: 9.112, year: 2014

Several oligothymidylates containing various ratios of phosphodiester and isopolar 50-hydroxyphosphonate, 50-O-methylphosphonate and 30-O-methylphosphonate internucleotide linkages were examined with respect to their hybridization properties with oligoriboadenylates and their ability to induce RNA cleavage by ribonuclease H (RNase H). The results demonstrated that the increasing number of 50-hydroxyphosphonate or 50-Omethylphosphonate units in antisense oligonucleotides (AOs) significantly stabilizes the heteroduplexes, whereas 30-O-methylphosphonate AOs cause strong destabilization of the heteroduplexes. Only the heteroduplexes with 50-O-methylphosphonate units in the antisense strand exhibited a significant increase in Escherichia coli RNase H cleavage activity by up to 3-fold (depending on the ratio of phosphodiester and phosphonate linkages) in comparison with the natural heteroduplex. A similar increase in RNase H cleavage activity was also observed for heteroduplexes composed of miRNA191 and complementary AOs containing 50-O-methylphosphonate units. We propose for this type of AOs, working via the RNase H mechanism, the abbreviation MEPNA
Permanent Link: http://hdl.handle.net/11104/0233466