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11.
Petrova NS Meschaninova MI Venyaminova AG Zenkova MA Vlassov VV Chernolovskaya EL 《FEBS letters》2011,585(14):2352-2356
The thermodynamic properties of siRNA duplexes are important for their silencing activity. siRNAs with high thermodynamic stability of both the central part of the duplex and in the whole, usually display low silencing activity. Destabilization of the central part of the siRNA duplex could increase its silencing activity. However, mismatches located in the central part of the duplex could substantially decrease the amount of RNAi efficacy, hindering active RISC formation and function. In this study, we examined the impact of duplex destabilization by nucleotide substitutions in the central part (7-10 nt counting from the 5'-end of the antisense strand) of the nuclease-resistant siRNA on its silencing activity. 相似文献
12.
M. A. Zenkova N. L. Chumakova A. V. Vlassov N. I. Komarova A. G. Venyaminova V. V. Vlassov V. N. Silnikov 《Molecular Biology》2000,34(3):390-394
The mechanism of hydrolysis of RNA substrates—diribonucleoside monophosphate CpA and decaribonucleotide UUCAUGUAAA—by chemical
constructs functionally mimicking ribonuclease A was studied. It is shown that RNA cleavage by chemical RNases 2L2 and 2D3
proceeds similar to the RNase A-induced RNA hydrolysis through 2′,3′-cyclophosphate as an intermediate product. A comparison
of hydrolyses of CpA in water and D2O revealed an isotope effect (K
H/K
D=2.28), which implies acid-base catalysis at the limiting stage of the reaction. Two feasible mechanisms of RNA hydrolysis
by chemical RNases (linear and adjacent) are discussed. 相似文献
13.
14.
Petrova Kruglova NS Meschaninova MI Venyaminova AG Zenkova MA Vlassov VV Chernolovskaya EL 《Oligonucleotides》2010,20(6):297-308
The thermodynamic asymmetry of siRNA duplexes determines their silencing activity. Favorable asymmetry can be achieved by incorporation of mismatches into the 3' part of the sense strand, providing fork-siRNAs, which exhibit higher silencing activity and higher sensitivity to nucleases. Recently, we found that selective 2'-O-methyl modifications of the nuclease-sensitive sites of siRNA significantly improve its nuclease resistance without substantial loss of silencing activity. Here, we examined the impact of nucleotide mismatches and the number and location of 2'-O-methyl modifications on the silencing activity and nuclease resistance of anti-MDR1 siRNAs. We found that both nonmodified and selectively modified fork-siRNAs with 4 mismatches at the 3' end of the sense strand suppress the expression of target gene at lower effective concentrations than the parent siRNAs with classical duplex design. The selective modification of nuclease-sensitive sites significantly improved the stability of fork-siRNAs in the presence of serum. The selectively modified fork-siRNA duplexes provided inhibitory effect over a period of 12 days posttransfection, whereas the gene silencing activity of the nonmodified analogs expired within 6 days. Thus, selective chemical modifications and structural alteration of siRNA duplexes improve their silencing properties and significantly prolong the duration of their silencing effect. 相似文献
15.
Novopashina DS Sinyakov AN Ryabinin VA Venyaminova AG Halby L Sun JS Boutorine AS 《化学与生物多样性》2005,2(7):936-952
New conjugates of triplex-forming pyrimidine oligo(2'-O-methylribonucleotides) with one or two 'head-to-head' hairpin oligo(N-methylpyrrole carboxamide) minor-groove binders (MGBs) attached to the terminal phosphate of the oligonucleotides with a oligo(ethylene glycol) linker were synthesized. It was demonstrated that, under appropriate conditions, the conjugates form stable complexes with double-stranded DNA (dsDNA) similarly to triplex-forming oligo(deoxyribonucleotide) (TFO) conjugates containing 5-methylated cytosines. Kinetic and thermodynamic parameters of the complex formation were evaluated by gel-shift assay and thermal denaturation. Higher melting temperatures (Tm), faster complex formation, and lower dissociation constants (Kd) of the triple helices (6-7 nM) were observed for complexes of MGB-oligo(2'-O-methylribonucleotide) conjugates with the target dsDNA compared to the nonconjugated individual components. Interaction of MGB moieties with the HIV proviral DNA fragment was indicated by UV/VIS absorption changes at 320 nm in the melting curves. The introduction of thymidine via a 3',3'-type 'inverted' phosphodiester linkage at the 3'-end of oligo(2'-O-methylribonucleotide) conjugates (3'-protection) had no strong influence on triplex formation, but slightly affected complex stability. At pH 6.0, when one or two hairpin MGBs were attached to the oligonucleotide, both triplex formation and minor-groove binding played important roles in complex formation. When two 'head-to-head' oligo(N-methylpyrrole) ligands were attached to the same terminal phosphate of the oligonucleotide or the linker, binding was observed at pH >7.5 and at high temperatures (up to 74 degrees). However, under these conditions, binding was retained only by the MGB part of the conjugate. 相似文献
16.
M. A. Kuznetsova D. V. Pyshnyi M. N. Repkova A. G. Venyaminova 《Russian Journal of Bioorganic Chemistry》2000,26(1):69-70
Oligo(2′-O-tetrahydropyranylribonucleotides) and their analogues containing a 3′-3′-internucleotide bond at the 3′-terminus are nuclease-resistant
and possess rather high affinity toward RNA, the main target in the antisense approach. 相似文献
17.
Akhmetova E. A. Golyshev V. M. Vokhtantcev I. P. Meschaninova M. I. Venyaminova A. G. Novopashina D. S. 《Russian Journal of Bioorganic Chemistry》2021,47(2):496-504
Russian Journal of Bioorganic Chemistry - A photoactivatable CRISPR/Cas9 system consisting of the Cas9 protein, synthetic 102-nt sgRNA or a pair of guide crRNA/tracrRNA, and blocking photocleavable... 相似文献
18.
O.?A.?KrashenininaEmail author V.?S.?Fishman D.?S.?Novopashina A.?G.?Venyaminova 《Russian Journal of Bioorganic Chemistry》2017,43(3):259-269
New fluorescent excimer-forming 5′-bispyrene molecular beacons for the detection of RNA were designed. The probes are 2′-O-methyl RNAs containing 5′-bispyrenylmethylphosphorodiamidate group (bispyrene group) at the 5′-end and a fluorescence quencher (BHQ1) at the 3′-end. A comparative study of the fluorescent properties of the probes having different distance between 5′-bispyrene group and target RNA upon the formation of hybridization complex was performed. The probes with bispyrene group located in the close proximity to the duplex exhibit the greatest excimer fluorescence upon binding to a complementary the 43-nt target RNA, in contrast to the probes with 5′-bispyrene group at dangling end. The feasibility of the new probes for visualization of intracellular RNA was demonstrated using 28S rRNA as a target. The results obtained confirm that the probes proposed in the study can be used as selective tools for RNA detection. 相似文献
19.
A. S. Davydova M. A. Vorobyeva M. R. Kabilov N. V. Tikunova D. V. Pyshnyi A. G. Venyaminova 《Russian Journal of Bioorganic Chemistry》2017,43(1):58-63
Infectious diseases caused by bacterial or viral agents represent the major cause of human pathogenesis and mortality worldwide. A development of novel antibacterial therapeutics and diagnostic tools is a very acute task. The use of DNA and RNA aptamers targeted to certain bacteria could be a promising solution to this problem. Here, we propose a new protocol of selection of 2′-fluoro RNA aptamers capable to internalize into bacterial cells. Using whole-cell SELEX against Pseudomonas aeruginosa, enriched 2′-fluoro RNA library was obtained, and its sequencing and data analysis were fulfilled. It was found that the central region of predominating aptamer sequence is identical to the fragment of P. aeruginosa rRNA. A possibility of internalizing of this aptamer into bacterial cells is shown. It is hypothesized that aptamers could be internalized more effectively as heterodimeric complexes. 相似文献
20.
The solution structure of a 3'-phenazinium (Pzn) tethered DNA-RNA duplex with a dangling adenosine: r(5'G-AUUGAA3'):d(5'TCAATC3'-Pzn).
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T V Maltseva P Agback M N Repkova A G Venyaminova E M Ivanova A Sandstrm V F Zarytova J Chattopadhyaya 《Nucleic acids research》1994,22(25):5590-5599
The 3'-Pzn group tethered to an oligo-DNA stabilizes a DNA-RNA hybrid duplex structure by 13 degrees C compared to the natural counterpart. This report constitutes the first full study of the conformational features of a hybrid DNA-RNA duplex, which has been possible because of the unique stabilization of this rather small duplex by the tethered 3'-Pzn moiety (Tm approximately 40 degrees C from NMR). In this study, a total of 252 inter- and intra-strand torsional and distance constraints along with the full NOE relaxation matrix, taking into account the exchange process of imino and amino protons with water, have been used. The 3'-Pzn-promoted stabilization of the DNA-RNA hybrid duplex results in detailed local conformational characteristics such as the torsion angles of the backbone and sugar moieties that are close to the features of the other natural DNA-RNA hybrids (i.e. sugars of the RNA strand are 3'-endo, but the sugars of the DNA strand are intermediate between A- and B-forms of DNA, 72 degrees < P < 180 degrees; note however, that the sugars of our DNA strand have a C1-exo conformation: 131 degrees < P < 154 degrees). This study suggests that 3'-Pzn-tethered smaller oligo-DNA should serve the same purpose as a larger oligo-DNA as a antisense inhibitor of the viral mRNA. Additionally, these types of tethered oligos have been found to be relatively more resistant to the cellular nuclease. Moreover, they are taken up quite readily through the cellular membrane (14) compared to the natural counterparts. 相似文献