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Nucleic acid components group

Logo zespołu komponentów kwasów nukleinowych

The research focus of the Nucleic Acid Components team revolves around molecules involved in the transmission and expression of genetic information. By using chemically synthesized modified ribonucleosides and RNA oligomers, we aim to address scientific questions regarding the impact of natural or pathogenic nucleosides in tRNA, mt-tRNA, and mRNA on the biological activity of these molecules, particularly in the process of protein biosynthesis. The team is also involved in the medical application of nucleic acids, specifically in the synthesis of therapeutic nucleic acids based on siRNA technology. The team is led by prof. Grażyna Leszczyńska.

The specific research areas of the team include:

  • Developing new, efficient, and cost-effective methods for synthesizing modified nucleosides present in cellular RNA structures and their unnatural analogs
  • Synthesizing modified nucleosides as reference samples for studies on the identification of modified nucleosides in hydrolysates of isolated RNA molecules
  • Physicochemical and structural characterization of modified nucleosides, including comprehensive spectroscopic analysis
  • Investigating the transformation of modified nucleosides under conditions that mimic oxidative stress in cells
  • Synthesizing modified monomeric units correlated with RNA synthesis using the amidophosphoramidite method on a solid phase
  • Exploring new protocols for synthesizing modified RNA fragments using both classical methods and post-synthetic modification techniques
  • Studying the structural determinants of RNA molecules' biological activity (in collaboration with other scientific centers in Poland and worldwide through biophysical, structural, and biochemical studies)
  • Using modified RNA to track the dynamics of modified units in vitro, under the influence of enzymatic editing/metabolizing proteins
  • Using modified RNA to explain the molecular causes of diseases associated with the presence or absence of modified ribonucleosides in RNA molecules
  • Selecting inhibitors of pathogen replication whose developmental cycles require the presence of RNA molecules specific to these organisms
  • Synthesizing therapeutic oligoribonucleotides used to silence defective genes.
Treść (rozbudowana)
Selected papers

    1. Podskoczyj, K.; Kłos A.; Dziergowska, A.; Leszczyńska G. "Protection-free, two-step synthesis of C5-C functionalized pyrimidine nucleosides", Curr. Protocols, 2024, doi: 10.1002/cpz1.984.

    2. Podskoczyj, K.; Kłos A.; Drewniak Sz.; Leszczyńska G. Two-step conversion of uridine and cytidine to variously C5-C functionalized analogs. Org. Biomol. Chem., 2023, 21, 2809-2815.

    3. Szczupak P., Sierant M., Wielgus, E., Radzikowska-Cieciura, E., Kulik K., Krakowiak A., Kuwerska P., Leszczynska G., Nawrot B. Escherichia coli tRNA 2-selenouridine synthase (SelU): elucidation od substrate specificity to understand the role of S-geranyl-tRNA in the conversion of 2-thio- into 2-selenouridines in bacterial tRNA. Cells, 2022, 11, 1522.

    4. Skotnicki, K., Janik, I., Sadowska, K., Leszczynska, G., Bobrowski, K. Radiation-Induced Oxidation Reactions of 2-Selenouracil in Aqueous Solutions: Comparison with Sulfur Analog of Uracil. Molecules 2022, 27(1), 133.

    5. K. Kulik, K. Sadowska, E. Wielgus, B. Pacholczyk-Sienicka, E. Sochacka, B. Nawrot;  “2‑Selenouridine, a modified nucleoside of bacterial tRNAs, its reactivity in the presence of oxidizing and reducing reagents”; Int. J. Mol. Sci., 23, 7973, doi.org/10.3390/ijms23147973 (2022)

    6. K. Frankowska, E. Sochacka; „New efficient synthesis of tRNA related adenosines bearing the hydantoin ring (ct6A, ms2ct6A) by intramolecular cyclization of N6-(N-Boc-α-aminoacyl)-adenosine derivatives”; ChemBioChem, 23, e2021006 (2022)

    7. Podskoczyj K., Kulik, K., Wasko, J., Nawrot, B., Suzuki, T., Leszczynska, G. Synthesis and properties of the anticodon stem-loop of human mitochondria tRNAMet containing the disease-related G and m1G nucleosides at position 37. Chem.Commun., 2021, 57, 12540.

    8. K. Dębiec, E. Sochacka; “Efficient access to 3′-O-phosphoramidite derivatives of tRNA related N6-threonylcarbamoyladenosine (t6A) and 2-methylthio-N6-threonylcarbamoyl-adenosine (ms2t6A)”; RSC Advances, 11, 1992-1999 (2021)

    9. Zhou J, Lénon M, Ravanat JL, Touati N, Velours C, Podskoczyj K, Leszczynska G, Fontecave M, Barras F, Golinelli-Pimpaneau B “Iron-sulfur biology invades tRNA modification: the case of U34 sulfuration”. Nucleic Acids Res. 2021;49, 997-4007.

    10. Leszczynska G, Cypryk M, Gistynski B, Sadowska K, Herman P, Bujacz G, Lodyga-Chruscinska E, Sochacka E, Nawrot B. “C5-substituted 2-selenouridines  ensure efficient base pairing with guanosine; consequences for reading the NNG-3’ synonymous mRNA codons”, Int. J. Mol. Sci. 2020, 21, 2882-2905;

    11. Bartosik K, Debiec K, Czarnecka A, Sochacka E, Leszczynska G. „Synthesis of nucleobase-modified RNA oligonucleotides by post-synthetic approach”, Molecules, 2020, 25, 3344-3381.

    12. K. Kulik, K. Sadowska, E. Wielgus, B. Pacholczyk-Sienicka, E. Sochacka, B. Nawrot; “Different oxidation pathways of 2-selenouraci and 2-thiouracil, natural components of transfer RNA”; Int. J. Mol. Sci., 21, 5956, doi: 10.3390/ijms21175956 (2020)

    13. Debiec K, Matuszewski M, Podskoczyj K, Leszczynska G, Sochacka E. „Chemical synthesis of oligoribonucleotide (ASL of tRNALys T.brucei) containing a recently discovered cyclic form of 2-methylthio-N6-threonylcarbamoyladenosine (ms2ct6A).” Chem. Eur. J. 2019, 25, 13309-13317;

    14. Borowski R, Dziergowska A, Sochacka E, Leszczynska G. „Novel entry to the synthesis of (S)- and (R)-5-methoxycarbonylhydroxymethyluridines – diastereomeric pair of wobble tRNA nucleosides”, RSC Adv., 2019, 9, 40507-40512;

    15. Sierant M., Leszczynska G., Sadowska K., Komar P., Radzikowska-Cieciura E., Sochacka E., Nawrot B. “Escherichia coli tRNA 2-selenouridine synthase (SelU) converts S2U-RNA to Se2U-RNA via S-geranylated-intermediate”, FEBS Letters, 2018, 592, 2248–2258.

    16. Zhou Q., Vu Ngoc B.T, Leszczynska G., Stigliani J-L., Pratviel G. “Oxidation of 5-methylaminomethyl uridine (mnm5U) by oxone leads to aldonitrone derivatives.” Biomolecules, 2018, 8, pii: E145.

    17. L. P. Sarin, S.D. Kienast, J. Leufken, R.L. Ross, A. Dziergowska, K. Debiec, E. Sochacka, P.A. Limbach, Ch. Fufezan, H.C.A. Drexler, S.A. Leidel; “Nano LC-MS using capillary columns enables accurate quantification of modified ribonucleosides at low femtomol levels” RNA, 24, 1403–1417 (2018)

    18. M. Sierant, K. Kulik, E. Sochacka, R. Szewczyk, M. Sobczak, B. Nawrot; “Cytochrome c catalyzes the hydrogen peroxide assisted oxidative desulfuration of 2-thiouridines in transfer RNAs”; ChemBioChem. 19, 687-695 (2018)

    19. Sochacka E., Lodyga-Chruscinska E., Pawlak J., Cypryk M., Bartos P., Ebenryter-Olbinska K., Leszczynska G, Nawrot B. C5-substituents of uridines and 2-thiouridines present at the wobble position of tRNA determine the formation of their keto-enol or zwitterionic forms – a factor important for accuracy of reading of guanosine at the 3’-end of the mRNA codons. Nucleic Acids Res. 2017, 45, 4825-4836;

    20. Bartosik K., Sochacka E., Leszczynska G. Post-synthetic conversion of 5-pivaloyloxymethyluridine present in a support-bound RNA oligomer into biologically relevant derivatives of 5-methyluridine. Org. Biomol. Chem., 2017, 15, 2097-2103.

    21. M. Matuszewski, K. Debiec, E. Sochacka; “Efficient conversion of N6-threonylcarbamoyl-adenosine (t6A) into a tRNA native hydantoin cyclic form (ct6A) performed at nucleoside and oligoribonucleotide levels”; Chem. Commun., 47, 7945-7948 (2017)

    22. Leszczynska G., Sadowska K., Sierant M., Sobczak M., Nawrot B., Sochacka E. Reaction of S-geranyl-2-thiouracil modified oligonucleotides with alkyl amines leads to the N2-alkyl isocytosine derivatives. Org. Biomol. Chem., 2017, 15, 5332-5336.

    23. M. Matuszewski, J. Wojciechowski, K. Miyauchi, Z. Gdaniec, W. M. Wolf, T. Suzuki, E. Sochacka; “A hydantoin isoform of cyclic N6-threonylcarbamoyladenosine (ct6A) is present in tRNAs”;Nucleic Acids Res., 45, 2137-2149 (2017)

    24. . Kang, K. Miyauchi, M. Matuszewski, G.S. D’Almeida, M.A. T. Rubio, J.D. Alfonzo, K. Inoue, Y. Sakaguchi, T. Suzuki, E. Sochacka, T. Suzuki; “Identification of 2-methylthio cyclic N6-threonylcarbamoyladenosine (ms2ct6A) as a novel RNA modification at position 37 of tRNAs”;Nucleic Acids Res., 45, 2124-2136 (2017)

    25. Leszczynska G., Sadowska K., Bartos P., Nawrot B., Sochacka E., S-Geranylated 2-thiouridines of bacterial tRNAs: chemical synthesis and physicochemical properties. Eur. J. Org. Chem. 2016, 3482-3485;

    26. Sierant M., Leszczynska G., Sadowska K., Dziergowska A., Rozanski M., Sochacka E., Nawrot B. S-Geranyl-2-thiouridine wobble nucleosides of bacterial tRNAs; chemical and enzymatic synthesis of S-geranylated-RNAs and their physicochemical characterization. Nucleic Acids Res. 2016, 44, 10986-10998;

    27. Duechler M., Leszczynska G., Sochacka E., Nawrot B. Nucleoside modifications in the regulation of gene expression: focus on tRNA. Cell Mol Life Sci. 2016, 73, 3075-3095;

    28. Bartosik K., Leszczynska G. Synthesis of various substituted 5-methyluridines (xm5U) and 2-thiouridines (xm5s2U) via nucleophilic substitution of 5-pivaloyloxymethyluridine/2-thiouridine.Tetrahedron Lett., 2015, 56, 6593-6597.

    29. Graham W.D., Barley-Maloney L., Stark C.J., Kaur A., Stolyarchuk K., Sproat B., Leszczynska G., Malkiewicz A., Safwat N., Mucha P., Guenther R., Agris P. F. Functional recognition of the modified human tRNALys3UUU anticodon domain by HIV's nucleocapsid protein and a peptide mimic. J. Mol. Biol., 2011, 410, 698-715;

    30. van den Born E., Vågbø C. B., Songe-Møller L., Leihne V., Lien G. F., Leszczynska G., Malkiewicz A., Krokan H.E., Kirpekar F., Klungland A., Falnes P.Ø. ALKBH8-mediated formation of a novel diastereomeric pair of wobble nucleosides in mammalian tRNA.  Nat. Commun., 2011, 2, 172, 

    31. Eshete M., Marchbank M.T., Deutscher S.L., Sproat B., Leszczynska G., Malkiewicz A., Agris P.F. Specificity of phage display selected peptides for modified anticodon stem and loop domains of tRNA. Protein J., 2007, 26, 61-73;

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