Ekaterina Anatolevna Burakova

Novosibirsk State University

Nowadays, nucleic acid derivatives capable of modulating gene expression at the RNA level have gained widespread recognition as promising therapeutic agents. A suitable degree of biological stability of oligonucleotide therapeutics is required for in vivo application; this can be most expeditiously achieved by the chemical modification of the inter...

Control of immune response following transplantation of cells, tissues, or organs includes reduction negative effects caused by acute graft-versus-host disease (GVHD) developing during bone marrow transplantation, thus being an urgent task of modern clinical practice. In this view, the management of immunological tolerance is a promising approach,...

Nowadays, nucleic acid derivatives capable of modulating gene expression at the RNA level gained widespread recognition as promising therapeutic agents. A suitable degree of biological stability of oligonucleotide therapeutics that is required for in vivo application can be most expeditiously achieved by chemical modification of the internucleotidi...

Staudinger reaction on the solid phase between an electronodeficit organic azide, such as sulfonyl azide, and the phosphite triester formed upon phosphoramidite coupling is a convenient method for the chemical modification of oligonucleotides at the internucleotidic phosphate position. In this work, 4-carboxybenzenesulfonyl azide, either with a fre...

A Staudinger reaction on solid phase between an electronodeficit organic azide such as sulfonyl azide, and the phosphite triester formed upon phosphoramidite coupling is a convenient method for chemical modification of oligonucleotides at the internucleotidic phosphate position. In this work, 4-carboxybenzenesulfonyl azide either with a free carbox...

New zwitter-ionic oligonucleotide derivatives containing 1,2,3,4-tetrahydroisoquinoline-7-sulfonyl phosphoramidate group are described. Automated synthesis of these compounds was carried out according to the β-cyanoethyl phosphoramidite scheme via the Staudinger reaction between 2-trifluoroacetyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonyl azide and...

New zwitter-ionic oligonucleotide derivatives containing 1,2,3,4-tetrahydroisoquinoline-7-sulfonyl phosphoramidate group are described. Automated synthesis of these compounds was carried out according to the β-cyanoethyl phosphoramidite scheme using the Staudinger reaction between 2-trifluoroacetyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonyl azide an...

To overcome immune tolerance to cancer, the immune system needs to be exposed to a multi-target action intervention. Here, we investigated the activating effect of CpG oligodeoxynucleotides (ODNs), mesyl phosphoramidate CpG ODNs, anti-OX40 antibodies, and OX40 RNA aptamers on major populations of immunocompetent cells ex vivo. Comparative analysis...

Rational combinations of sequence-specific inhibitors of pro-oncogenic miRNAs can efficiently interfere with specific tumor survival pathways, offering great promise for targeted therapy of oncological diseases. Herein, we uncovered the potential of multicomponent therapy by double or triple combinations of highly potent mesyl phosphoramidate (µ) a...

Tyrosyl-DNA phosphodiesterase 1 (TDP1) catalyzes the cleavage of the phosphodiester bond between the tyrosine residue of topoisomerase 1 (TOP1) and the 3′ phosphate of DNA in the single-strand break generated by TOP1. TDP1 promotes the cleavage of the stable DNA–TOP1 complexes with the TOP1 inhibitor topotecan, which is a clinically used anticancer...

Background/aim: We compared the therapeutic efficacy of two recently developed experimental anticancer technologies: 1) in situ vaccination based on local immunotherapy with CpG oligonucleotides and anti-OX40 antibodies to activate antitumor immune response and 2) "Karanahan" technology [from the Sanskrit kāraṇa ('source') + han ('to kill')] based...

We have proposed previously a template-assisted method for 3D assembly of nucleic acid nanostructures. The method involved a branched oligonucleotide as a template and a building block, which incorporates non-nucleotidic linkers, in particular, branching foci connecting two or three oligonucleotide chains. In this work, we have attempted the synthe...

Myeloid dendritic cells (DCs) play an important role in the immune response; therefore, the search for compounds that can effectively activate DCs is a needful goal. This study was aimed to investigate the effect of synthetic CpG oligodeoxynucleotides (CpG-ODN) on the maturation and allostimulatory activity of myeloid DCs in comparison with other P...

Recently, three-dimensional nucleic acid nanostructures have attracted great interest, which have been made available through the DNA origami technique. We have proposed a different way of constructing nucleic acid nanoobjects, namely, template-directed assembly employing branched oligonucleotides as templates and building blocks, which include non...

The worldwide spread of multidrug-resistant Mycobacterium tuberculosis strains prompted the development of new strategies to combat tuberculosis, one of which is antisense therapy based on targeting bacterial mRNA by oligonucleotide derivatives. However, the main limitation of antisense antibacterials is poor cellular uptake because of electrostati...

The effect of phosphate group modifications on formation and properties of G‐quadruplexes (G4s) has not been investigated in detail. Here, we evaluated the structural, thermodynamic and kinetic properties of the parallel G‐quadruplexes formed by oligodeoxynucleotides d(G4T), d(TG4T) and d(TG5T), in which all phosphates were replaced with N‐methanes...

Significance Forty years of research have shown that antisense oligonucleotides have great potential to target mRNAs of disease-associated genes and noncoding RNAs. Among the vast number of oligonucleotide backbone modifications, phosphorothioate modification is the most widely used in research and the clinic. However, along with their merits are n...

Analysis and isolation of new charge-neutral phosphoryl guanidine oligonucleotides (PGO) by vertical slab electrophoresis were tested at different pH values (3-11) or in the presence of SDS as a micelle-forming agent. The most convenient way to analyze and purify phosphoryl guanidine oligonucleotides was by denaturing PAGE (8 M urea) at pH 3. The m...

Novel oligonucleotide derivatives containing N-(methanesulfonyl)-phosphoramidate (mesyl phosphoramidate) group have been described. Solid-phase synthesis of these compounds using an automated DNA synthesizer has been performed for the first time, including the Staudinger reaction between methanesulfonyl azide (mesyl azide) and 3′,5′-dinucleoside 2-...

We describe an approach to the synthesis of TaqMan oligonucleotide probes that is based on Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click chemistry when oligonucleotides containing an internal alkynyl group at the pyrimidine position are labeled post-synthetically with a f luorescent azide. TaqMan probes were constructed with f luorescein...

N-Sulfonyl phosphoramidate derivatives of oligodeoxyribonucleotides containing N-tosyl phosphoramidate groups are first reported. The synthesis is based on Staudinger reaction between tosyl azide and 3′,5′-dinucleoside β-cyanoethyl phosphite comprising the immobilized oligonucleotide, which is obtained by the phosphoramidite coupling during the sol...

Artificial ribonucleases (aRNases) are small compounds catalysing RNA cleavage. Recently we demonstrated that aRNases readily inactivate various viruses in vitro. Here, for three series of aRNases (1,4-diazabicyclo [2.2.2]octane-based and peptide-like compounds) we show that apart from ribonuclease activity the aRNases display chaotropic-like and m...

Antibacterial activity of tetracationic compounds based on 1,4-diazabicyclo[2.2.2]octane (DABCO) bis-quaternary salts with dodecyl substituents bound by linker groups containing four carbon atoms was studied. All the compounds exhibited activity against the test-strains under study. The gram-positive culture S. aureus was found to be the most sensi...

SUBSTANCE: method involves administering into the poultry the polycationic compound 1,5-bis-(4- tetradecyl-1,4-diazoniabicyclo[2.2.2]octan-1-yl)pentan tetrabromide dissolved in 85% formic acid with reducing the concentration to 3 gram per 1 litre of the acid; then the mother solution is diluted with tap water to the concentration of the mother solu...

FIELD: medicine, pharmaceutics. SUBSTANCE: invention refers to medicine, namely to broad-spectrum antibacterial preparations. What is presented is an agent representing sodium dihydroxocystine diaminodiargenate possessing the antibacterial activity. The agent represents a complex C6H12Ag2N2Na2O6S2 of two silver ions with a disodium salt of natural...

FIELD: chemistry. SUBSTANCE: method for synthesis of a 1,5-bis-(4-tetradecyl-1,4-diazoniabicyclo[2.2.2]octan-1-yl)pentane tetrabromide (C47H100Br4N4) derivative includes dissolving 1-tetradecyl-4-aza-1-azoniabicyclo[2.2.2]octane bromide in methanol while heating to temperature of 55°C, while stirring, adding two portions 1,5-dibromomethane to the o...

2-(3,5-Bis{[1,5,9-tris(trifluoroacetyl)-1,5,9-triazacyclododecan-3-yloxy]methyl}phenoxy)ethanol was synthesized and converted to a O-(2-cyanoethyl)-N,N-diisopropylphosphoramidite building block, 12. 2’- O-Methyl oligoribonucleotides incorporating a 2-[(2S,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran- 2-yl)ethyl 4-oxopentanoate or a 2-{2-[2-({[...

The acute toxicity and antiviral activity of synthetic ribonucleases with various structures have been studied. It is established that synthetic ribonucleases exhibit low toxicity with respect to MDCK cell cultures and inhibit to different extents the reproduction of influenza A and B type viruses.

A number of tetracationic compounds capable of phosphodiester bond cleavage within a 21 -membered ribooligonucleotide were designed and synthesized. The artificial ribonucleases represent two residues of quaternized 1,4-diazabicyclo[2.2.2]octane bearing alkyl substituents of various lengths and connected with a rigid linker. The efficiency of cleav...

Combinatorial libraries of small organic compounds capable of cleaving RNA were synthesized. The compounds contain benzene ring substituted with two residues of bis quaternary salt of diazabicyclo[2.2.2]octane (DABCO) bearing hydrophobic fragments of different length and structure, attached to DABCO at the bridge position. These compounds, lacking...

A number of small organic ribonucleases have been synthesized with rigid polycationic structures containing an aromatic framework with two residues of bis-quaternary salts of 1,4-diazabicyclo[2.2.2]octane (DABCO) bearing various substituents. The compounds carrying positively charged groups connected via rigid linker are expected to bend the sugar-...

Cationic compounds containing benzene ring substituted with the bis-quaternary salt of diazabicyclo[2.2.2]octane (DABCO) bearing a polymethylene fragment at the bridge positions display ribonuclease activity. Efficacy of the catalysis is affected by geometry of the cationic structures and the size of the attached aliphatic fragment. The cleavage oc...

2,2-Dimethyl-3-(2-methyl-3-indolyl)cyclopropylacetic acid, its amide and esters, and the corresponding alcohol, viz., the product of ester reduction by LiAlH4, were synthesized. The chemoselectivity of N- and O-alkylation of these compounds was studied. Selective monoalkylation at the nitrogen atom of the heterocycle, O-alkylation to the side chain...