Аралов Андрей Владимирович

Кандидат химических наук


Руководитель подразделения (Группа молекулярных инструментов для исследования живых систем)

Эл. почта: Baruh238@mail.ru

Избранные публикации

  1. Tsvetkov V.B., Zatsepin T.S., Belyaev E.S., Kostyukevich Y.I., Shpakovski G.V., Podgorsky V.V., Pozmogova G.E., Varizhuk A.M., Aralov A.V. (2018). i-Clamp phenoxazine for the fine tuning of DNA i-motif stability. Nucleic Acids Res. 46 (6), 2751–2764 [+]

    Non-canonical DNA structures are widely used for regulation of gene expression, in DNA nanotechnology and for the development of new DNA-based sensors. I-motifs (iMs) are two intercalated parallel duplexes that are held together by hemiprotonated C-C base pairs. Previously, iMs were used as an accurate sensor for intracellular pH measurements. However, iM stability is moderate, which in turn limits its in vivo applications. Here, we report the rational design of a new substituted phenoxazine 2'-deoxynucleotide (i-clamp) for iM stabilization. This residue contains a C8-aminopropyl tether that interacts with the phosphate group within the neighboring chain without compromising base pairing. We studied the influence of i-clamp on pH-dependent stability for intra- and intermolecular iM structures and found the optimal positions for modification. Two i-clamps on opposite strands provide thermal stabilization up to 10-11°C at a pH of 5.8. Thus, we developed a new modification that shows significant iM-stabilizing effect both at strongly and mildly acidic pH and increases iM transition pH values. i-Clamp can be used for tuning iM-based pH probes or assembling extra stable iM structures for various applications.

    ID:2074
  2. Shpakovski G.V., Spivak S.G., Berdichevets I.N., Babak O.G., Kubrak S.V., Kilchevsky A.V., Aralov A.V., Slovokhotov I.Y., Shpakovski D.G., Baranova E.N., Khaliluev M.R., Shematorova E.K. (2017). A key enzyme of animal steroidogenesis can function in plants enhancing their immunity and accelerating the processes of growth and development. BMC Plant Biol. 17 (Suppl 1), 189 [+]

    The initial stage of the biosynthesis of steroid hormones in animals occurs in the mitochondria of steroidogenic tissues, where cytochrome P450SCC (CYP11A1) encoded by the CYP11A1 gene catalyzes the conversion of cholesterol into pregnenolone - the general precursor of all the steroid hormones, starting with progesterone. This stage is missing in plants where mitochondrial cytochromes P450 (the mito CYP clan) have not been found. Generating transgenic plants with a mitochondrial type P450 from animals would offer an interesting option to verify whether plant mitochondria could serve as another site of P450 monooxygenase reaction for the steroid hormones biosynthesis.

    ID:1982
  3. Varizhuk A.M., Zatsepin T.S., Golovin A.V., Belyaev E.S., Kostyukevich Y.I., Dedkov V.G., Shipulin G.A., Shpakovski G.V., Aralov A.V. (2017). Synthesis of oligonucleotides containing novel G-clamp analogue with C8-tethered group in phenoxazine ring: Implication to qPCR detection of the low-copy Kemerovo virus dsRNA. Bioorg. Med. Chem. 25 (14), 3597–3605 [+]

    Nowadays modified oligonucleotides are widely used in diagnostics and as novel therapeutics. Introduction of modified or unnatural residues into oligonucleotides allows fine tuning of their binding properties to complementary nucleic acids and leads to improved stability both in vitro and in vivo. Previously it was demonstrated that insertion of phenoxazine nucleotides with various groups in C9-position into oligonucleotides leads to a significant increase of duplex stability with complementary DNA and RNA. Here the synthesis of a novel G-clamp nucleoside analogue (G(8AE)-clamp) bearing 2-aminoethyl tether at C8-atom is presented. Introduction of such modified residues into oligonucleotides lead to enhanced specificity of duplex formation towards complementary DNA and RNA targets with increased thermal and 3'-exonuclease stability. According to CD-spectroscopy studies G(8AE)-clamp does not substantially disrupt helix geometry. Primers containing G(8AE)-clamp demonstrated superior sensitivity in qPCR detection of dsRNA of Kemerovo virus in comparison to native oligonucleotides.

    ID:1819
  4. Aralov A.V., Proskurin G.V., Orlov A.A., Kozlovskaya L.I., Chistov A.A., Kutyakov S.V., Karganova G.G., Palyulin V.A., Osolodkin D.I., Korshun V.A. (2017). Perylenyltriazoles inhibit reproduction of enveloped viruses. European journal of medicinal chemistry 138, 293–299 [+]

    1-Substituted 4-perylen-2(3)-yl-1,2,3-triazoles, easily accessible by 'click' reaction and combining in one molecule a polyaromatic unit and a nitrogen heterocycle, were found to strongly inhibit the reproduction of enveloped viruses. 5-[4-(Perylen-3-yl)-1,2,3-triazol-1-yl]-uridine and 2-[1-(2-hydroxyethyl)-1,2,3-triazol-4-yl]perylene show EC50 of 0.031 and 0.023 μM, respectively, against tick-borne encephalitis virus (TBEV). Remarkably, the nucleoside unit appears to be not essential for antiviral activity. These results provide deeper understanding of structural basis of activity for this new class of antivirals.

    ID:1820
  5. Efimov V.A., Aralov A.V., Klykov V.N., Chakhmakhcheva O.G. (2009). Synthesis of RNA by the rapid phosphotriester method using azido-based 2'-O-protecting groups. Nucleosides Nucleotides Nucleic Acids 28 (9), 846–65 [+]

    The azidomethyl and 2-(azidomethyl)benzoyl as 2'-OH protecting groups are reported for preparation of oligoribonucleotides by the phosphotriester solid-phase method using O-nucleophilic intramolecular catalysis. The procedures for the synthesis of the corresponding monomer synthons were developed and the usefulness of the application of 2'-O-azidomethyl and 2'-O-2-(azidomethyl)benzoyl groups was examined in the synthesis of different RNA fragments with a chain length of 15-22 nucleotides. The azidomethyl group was found to be more preferable for effective synthesis of oligoribonucleotides. Hybridization properties of RNAs toward their complementary oligonucleotides were examined before and after the removal of 2'-O-azidomethyl groups.

    ID:1827
  6. Aralov A.V., Chakhmakhchieva O.G. (2009). [Protection of 2'-hydroxyls in the chemical synthesis of oligoribonucleotides]. Bioorg. Khim. 39 (1), 3–25 [+]

    The review is devoted to the chemical synthesis of oligoribonucleotides and the protecting groups used. In particular the existent methods of blocking 2'-OH function in nucleotide monomers for the RNA synthesis are discussed in detail.

    ID:1821
  7. Aralov A.V., Klykov V.N., Chakhmakhcheva O.G., Efimov V.A. (2009). [Monomers containing 2'-o-alkoxymethyl groups as synthons for the synthesis of oligoribonucleotides by the phosphotriester method]. Bioorg. Khim. 37 (5), 654–61 [+]

    A general scheme for the synthesis of ribonucleotide monomers containing alkoxymethyl group in 2'-O-position for the solid-phase phosphotriester oligonucleotide synthesis using O-nucleophilic intramolecular catalysis has been developed. In particular, the monomers containing 2'-O-modifying 2-azidoethoxymethyl, propargyloxymethyl, or 3,4-cyclocarbonatebutoxymethyl groups has been prepared.

    ID:1822
  8. Efimov V.A., Aralov A.V., Chakhmakhcheva O.G. (2009). Synthesis of oligoribonucleotides containing 2'-O-methoxymethyl group by the phosphotriester method. Nucleosides Nucleotides Nucleic Acids 30 (7-8), 565–76 [+]

    An effective procedure for the synthesis of ribonucleotide monomers containing a 2 '-О-methoxymethyl-modifying group was developed. These monomers were used for the synthesis of RNA fragments by the solid-phase phosphotriester method under O-nucleophilic intramolecular catalysis. The properties of 2 '-О-methoxymethyl-containing oligoribonucleotides were examined.

    ID:1823
  9. Efimov V.A., Aralov A.V., Chakhmakhcheva O.G. (2009). [Methoxymethyl and (p-nitrobenzyloxy)methyl groups in the synthesis of oligoribonucleotides by the phosphotriester method]. Bioorg. Khim. 37 (2), 284–8 [+]

    An efficient synthetic method for monomer ribonucleotide synthons containing 2'-O-methoxymethyl and 2'O-(p-nitrobenzyloxy)methyl groups used for oligonucleotide phosphotriester method with O-nucleophilic intramolecular catalysis at the stage of formation of internucleotide bond is developed. It is shown that synthons containing protecting 2'-O-(p-nitrobenzyloxy)methyl group may be used for automatic synthesis of phosphotriester oligoribonucleotides with high yields and synthons containing methoxymethyl group--to get 2'-O-modified oligonucleotides.

    ID:1824
  10. Efimov V.A., Aralov A.V., Chakhmakhcheva O.G. (2009). [DNA mimics on the base of pyrrolidine and hydroxyproline]. Bioorg. Khim. 36 (6), 725–46 [+]

    In order to improve physicochemical and biological properties of natural oligonucleotides in particular increasing their affinity for nucleic acids, the selectivity of action and biological sustainability, several types of DNA mimics were designed. The survey collected data on the synthesis and properties of the DNA mimics - peptide-nucleic acids analogues, which are derivatives of pyrrolidine and hydroxyproline. We examine some physicochemical and biological properties of negatively charged mimics of this type, containing phosphonate residues, and possessing a high affinity for DNA and RNA, selective binding with nucleic acids and stability in various biological systems. Examples of the use of these mimics as tools for molecular biological research, particularly in functional genomics are given. The prospects for their use in diagnostics and medicine are discussed.

    ID:1825
  11. Efimov V.A., Aralov A.V., Grachev S.A., Chakhmakhcheva O.G. (2009). [N-azidomethylbenzoyl blocking group in the phosphotriester synthesis of oligonucleotides]. Bioorg. Khim. 36 (5), 681–7 [+]

    An effective modification of phosphotriester method for automatic synthesis of DNA and RNA fragments using O-nucleophilic intramolecular catalysis and 2-(azidometil)benzoyl group to protect amino groups of heterocyclic bases of nucleotides is described.

    ID:1826
  12. Efimov V.A., Aralov A.V., Fediunin S.V., Klykov V.N., Chakhmakhcheva O.G. (2009). [An azidomethyl protective group in the synthesis of oligoribonucleotides by the phosphotriester method]. Bioorg. Khim. 35 (2), 270–3 [+]

    A rapid and effective method of an automatic oligoribonucleotide synthesis alternative to the phosphoroamidite one was developed based on the phosphotriester approach of internucleotide bond formation under intramolecular O-nucleophilic catalysis and the use of an azidomethyl group for protection of a nucleotide 2'-hydroxyl function.

    ID:1828