title: 5'-O-Methylphosphonate nucleic acids--new modified DNAs that increase the Escherichia coli RNase H cleavage rate of hybrid duplexes.
abstract: Several oligothymidylates containing various ratios of phosphodiester and isopolar 5'-hydroxyphosphonate, 5'-O-methylphosphonate and 3'-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 5'-hydroxyphosphonate or 5'-O-methylphosphonate units in antisense oligonucleotides (AOs) significantly stabilizes the heteroduplexes, whereas 3'-O-methylphosphonate AOs cause strong destabilization of the heteroduplexes. Only the heteroduplexes with 5'-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 5'-O-methylphosphonate units. We propose for this type of AOs, working via the RNase H mechanism, the abbreviation MEPNA (MEthylPhosphonate Nucleic Acid).
authors: Institute of Photonics and Electronics AS CR, v.v.i., Chaberská 57, 182 51 Prague, Czech Republic, Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nám. 2., 166 10 Prague, Czech Republic and Faculty of Mathematics and Physics, Charles University in Prague, Ke Karlovu 3, 121 16 Prague, Czech Republic.
authors: Hana
authors: H
authors: Šipova
authors: Tomaš
authors: T
authors: Špringer
authors: Dominik
authors: D
authors: Rejman
authors: Ondřej
authors: O
authors: Šimak
authors: Magdalena
authors: M
authors: Petrová
authors: Pavel
authors: P
authors: Novák
authors: Šarka
authors: Š
authors: Rosenbergová
authors: Ondřej
authors: O
authors: Páv
authors: Radek
authors: R
authors: Liboska
authors: Ivan
authors: I
authors: Barvík
authors: Josef
authors: J
authors: Štěpanek
authors: Ivan
authors: I
authors: Rosenberg
authors: Jiři
authors: J
authors: Homola
mesh_terms: D004926:Escherichia coli / Q000201:enzymology*; D035683:MicroRNAs / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000737:chemistry*; D063065:Organophosphonates / Q000737:chemistry*; D059367:RNA Cleavage; D016914:Ribonuclease H / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D063065:Organophosphonates; D016914:Ribonuclease H