A route to 2′,5′‐oligoadenylates with increased stability towards phosphodiesterases

Itkes, A.V.; Karpeisky, M.Ya.; Kartasheva, O.N.; Mikhailov, Sergey N.; Moiseyev, Gennady P.; Pfleiderer, Wolfgang; Charubala, Ramamurthy; Yakovlev, G. I.

doi:10.1016/0014-5793(88)80048-6

Cited by 13 publications

(7 citation statements)

References 8 publications

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“…The principal components of the four-charge and longer fractions were observed to be in a cluster of more intense peaks with the longer retention times on the reverse phase column. The extent of the MepA-initiation of these oligomers was determined by phosphodiesterase I (PD I) hydrolysis which cleaves 3 ,5 -; 2 ,5 -and 5 ,5 -phosphodiester bonds (Richards et al, 1967;Itkes et al., 1988). PD I also cleaves the methyl grouping from MepA to give adenosine and 5 -AMP but at a slower rate than it cleaves the phosphodiester bond between nucleotides.…”

Section: Reaction Of Mepa With Impumentioning

confidence: 99%

See 1 more Smart Citation

Catalysis and Selectivity in Prebiotic Synthesis: Initiation of the Formation of Oligo(U)s on Montmorillonite Clay by Adenosine-5′-methylphosphate

Wang

Ferris

2005

Orig Life Evol Biosph

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Adenosine-5'-methylphosphate (MepA) initiates the oligomerization of the 5'-phosphorimidazolide of uridine (ImpU) in the presence of montmorillonite clay. Longer oligomers form because the 5'-phosphate is blocked with a methyl group that prevents the formation of cyclic- and pyrophosphate-containing compounds. The MepA initiates 69-84% of the 5-9 charge oligomers, respectively. The montmorillonite catalyst also provides selectivity in the oligomerization reactions so that the main reaction pathway is MepA --> MepA3'pU --> MepA3'pU2'pU --> MepA3'pU2'pU3'pU. MepA did not enhance the oligomerization of ImpA. The relative rates of the reactions were determined from an investigation of the products in competitive reactions. Selectivity was observed in the reaction of ImpU with equimolar amounts of MepA3'pU and MepA2'pU where the relative reaction rates are 10.3:1, respectively. In the reaction of ImpA with MepA3'pA and MepA2'pA the ImpA reacts 5.2 times faster with MepA3'pA. In the competitive reaction of ImpU and ImpA with MepA3'pA and MepA3'pU the elongation proceeds on MepA3'pA 5.6 times more rapidly than with MepA3'pU. There is no correlation between the extent of binding to the montmorillonite and reaction rates in the formation of longer oligomers. The formation of more than two sequential 2',5'-linkages in the oligomer chain proceeds more slowly than the addition to a single 2',5'-link or a 3',5'-link and either chain termination or elongation by a 3',5'-linage occurs. The central role that catalysis may have had in the prebiotic formation of biopolymers is discussed.

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Section: Reaction Of Mepa With Impumentioning

confidence: 99%

“…It was found that in addition to 3 ,5 -linkages, 2 ,5 -linkages and 5 ,5 -linkages, PD I cleaved the methyl phosphate group of MepA to 5 -AMP (Richards et al, 1967;Itkes et al, 1988). The substrate was dissolved in 0.11 M Tris, 0.11 M NaCl and 0.015 M MgCl 2 (pH 9.0) as described in the 1988 Worthington manual, page 269.…”

Section: Generalmentioning

confidence: 99%

Catalysis and Selectivity in Prebiotic Synthesis: Initiation of the Formation of Oligo(U)s on Montmorillonite Clay by Adenosine-5′-methylphosphate

Wang

Ferris

2005

Orig Life Evol Biosph

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“…This is also mirrored in the destabilizing effects of UNA-incorporation in duplexes, with up to 12 °C decrease in T m per UNA monomer in RNA:RNA duplexes and 10 °C per UNA monomer in RNA:DNA duplexes [ 6 ]. Incubation of a UNA A tri-mer with SVPD or in cell lysate indicates that UNA is also highly resistant to nucleases [ 89 ]. UNA monomers have proven very useful in fine-tuning the specificity and potency of siRNA, in particularly in combination with LNA [ 90 , 91 , 92 ].…”

Section: Unlocked Nucleic Acidsmentioning

confidence: 99%

Locked and Unlocked Nucleosides in Functional Nucleic Acids

Doessing

Vester

2011

Molecules

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Nucleic acids are able to adopt a plethora of structures, many of which are of interest in therapeutics, bio- or nanotechnology. However, structural and biochemical stability is a major concern which has been addressed by incorporating a range of modifications and nucleoside derivatives. This review summarizes the use of locked nucleic acid (LNA) and un-locked nucleic acid (UNA) monomers in functional nucleic acids such as aptamers, ribozymes, and DNAzymes.

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“…The possibilities to use phosphorylated trioligoadenylate are limited, since this compound, because of its high polarity, cannot enter eukaryotic cells. Dephosphorylated trioligoadenylate (2′,5′ApApA), due to its rather high ability to penetrate the cellular membrane [12], demonstrates significant biological activity upon its immediate addition to the culture medium. The effects of this compound (both antiviral [13] and antiproliferative [14]) are analogous to those observed in the case where the level of endogenous 2′-5′А is increased.…”

Section: Introductionmentioning

confidence: 99%

Effect of dephosphorylated 2′,5′-trioligoadenylate on the entry of sodium ions into human neuroblastoma cells

et al. 2008

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Using a radioisotope technique, we studied the effect of dephosphorylated 2′,5′-trioligoadenylate (2′,5′ApApA) on the entry of sodium ions into cultured human neuroblastoma cells (IMR 32 strain). Short-term (nearly 1 h) action of 2′,5′ApApA did not influence the entry of sodium ions through voltage-operated sodium channels in the absence of neurotoxins modulating the characteristics of these channels (toxin of a scorpion, Leiurus quinquestriatus, + veratrine). At the same time, 2′,5′АрАрА weakened in a dose-dependent manner the entry of sodium ions through sodium channels opened upon the action of the above neurotoxins. In cells cultured for 22 h in a medium containing 5·10 -6 M 2′,5′ApApA, the entry of sodium ions in the absence of neurotoxins was 25% greater, while in the presence of neurotoxins it was 24% smaller than that in the control cells. Tetrodotoxin (ТТХ, 4 ·10 −7 M) blocked completely sodium entry through sodium channels in cells cultured in the absence of 2′,5′ApApA, while in cells cultured in the presence of this adenylate TTX decreased the entry by 64%. It is hypothesized that long-lasting action of 2′,5′ApApA results in the appearance of voltageoperated TTX-insensitive sodium channels in the plasma membrane of IMR 32 cells. Our data show that 2′,5′ApApA is capable of modulating to a considerable extent the functioning of mechanisms controlling transport of sodium ions in cells of human neuroblastoma cells of the IMR 32 strain.

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A route to 2′,5′‐oligoadenylates with increased stability towards phosphodiesterases

Cited by 13 publications

References 8 publications

Catalysis and Selectivity in Prebiotic Synthesis: Initiation of the Formation of Oligo(U)s on Montmorillonite Clay by Adenosine-5′-methylphosphate

Catalysis and Selectivity in Prebiotic Synthesis: Initiation of the Formation of Oligo(U)s on Montmorillonite Clay by Adenosine-5′-methylphosphate

Locked and Unlocked Nucleosides in Functional Nucleic Acids

Effect of dephosphorylated 2′,5′-trioligoadenylate on the entry of sodium ions into human neuroblastoma cells

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