Our team focuses on the design and synthesis of modified nucleosides, nucleotides, and oligonucleotides with potential therapeutic applications. We introduce structural modifications that enhance the stability, selectivity, and biological activity of the molecules we produce. Our approach integrates organic synthesis, nucleic acid chemistry, and biophysical methods. In our work, we employ stereocontrolled phosphorus chemistry, advanced purification techniques, and structural analysis methods such as NMR, circular dichroism (CD) spectroscopy, and X-ray crystallography.
Our research is interdisciplinary, bridging chemistry and molecular biology. We actively collaborate with international scientific partners (University of Colorado Boulder, Murdoch University) to evaluate the biological relevance of the synthesized compounds, with a particular focus on therapeutic nucleic acids.
Our team includes PhD students, Master’s students, and interns, all of whom participate in different stages of research projects. Through inter-university collaboration, we enable the completion of Bachelor’s, engineering, and Master’s theses. We place strong emphasis on mentoring and scientific development, providing young researchers with hands-on experience in advanced synthesis and analytical techniques. Our students actively engage in the entire research process, from experiment planning and execution to data analysis and preparation of scientific publications. Participation in conferences helps them develop presentation skills and build professional scientific networks, preparing them for independent research careers.
Principal Investigator: dr Katarzyna Jastrzębska
Project: Grant NCN, SONATA 17
Number: 2021/43/D/ST4/02433
Opis projektu
Jastrzębska K., Jakubowska J., Szymańska A., Stępniak W., Pawlowska R., Chworos A., Biologically Relevant Morpholino Nucleoside Thio- and Dithiophosphates via an Oxathiaphospholane Approach, New J. Chem., 2025
Jastrzębska K., Szymańska A., Pawlak T., Dolot R., Morpholino-Based Phosphorothioate Analogs via Oxathiaphospholane Chemistry: Synthesis, Structural Insights and Stability, Org. Biomol. Chem., 2025
https://pubs.rsc.org/en/content/articlelanding/2025/ob/d5ob01223f
Jastrzębska K., Antończyk P., Dolot R., P-Stereodefined morpholino dinucleoside 3′,5′-phosphorothioates, Org. Biomol. Chem., 2024, 22, 8737-8742
Jastrzębska K., An efficient alternative to DBU in the oxathiaphospholane (OTP) method for the solid phase synthesis of P-stereodefined phosphorothioate analogs, RSC Advances, 2024, 14, 21174 – 21179
https://pubs.rsc.org/en/content/articlelanding/2024/ob/d4ob01437e
Le B. T., Paul S., Jastrzebska K., Langer H., Caruthers M.H., Veedu R.N., Thiomorpholino oligonucleotides as a robust class of next generation platforms for alternate mRNA splicing, PNAS, 2022, 119, 1-8
https://www.pnas.org/doi/10.1073/pnas.2207956119
Jastrzębska K., Maciaszek A., Dolot R., Tomaszewska-Antczak A., Mikołajczyk B., Guga P., Synthesis and hybridizing properties of P-stereodefined chimeric [PS]-{DNA:RNA} and [PS]-{DNA:(2′-OMe)-RNA} oligomers, RSC Adv., 2022, 12, 26815-26824
https://pubs.rsc.org/en/content/articlelanding/2022/ra/d2ra04855h
Dumbović G., Braunschweig U., K. Langner H., Smallegan M., Biayna J., Hass E.P., Jastrzebska K., Blencowe B., Cech T.R., Caruthers M.H., Rinn J.L., Nuclear compartmentalization of TERT mRNA and TUG1 lncRNA is driven by intron retention, Nature Comm. 2021, 12, 3308, 1-19
https://www.nature.com/articles/s41467-021-23221-w
Langner H., Jastrzebska K., Caruthers M., Synthesis and Characterization of Thiophosphoramidate Morpholino Oligonucleotides and Chimeras, J. Am. Chem. Soc. 2020, 142, 38, 16240–16253
https://pubs.acs.org/doi/10.1021/jacs.0c04335
Jastrzębska K., Mikołajczyk B., Guga P., LNA units present in [RP-PS]-(DNA#LNA) chimeras enhance the thermal stability of parallel duplexes and triplexes formed with (2′-OMe)-RNA strands, RSC Adv., 2020, 10, 22370-22376
https://pubs.rsc.org/en/content/articlelanding/2020/ra/d0ra03934a
Krishna H., Jastrzebska K., Caruthers M., Exploring site-specific activation of bis-N,N’-dialkylaminophosphordiamidites and the synthesis of morpholinophosphoramidate oligonucleotides, FEBS Lett., 2019, 593, 1459-1467
https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1873-3468.13492
Maciaszek A., Jastrzębska K., Guga P., Homopurine RP-stereodefined phosphorothioate analogs of DNA with hampered Watson-Crick base pairings form Hoogsteen paired parallel duplexes with (2′-OMe)-RNAs, Org. Biomol. Chem., 2019, 17, 4611-4620
https://pubs.rsc.org/en/content/articlelanding/2019/ob/c8ob03112f
Tomaszewska-Antczak A., Jastrzębska K., Maciaszek A., Mikołajczyk B., Guga P., P-Stereodefined phosphorothioate analogs of glycol nucleic acids – synthesis and structural properties, RSC Adv., 2018, 8, 24942-24952
https://pubs.rsc.org/en/content/articlelanding/2018/ra/c8ra05568h
Jastrzębska K., Maciaszek A., Dolot R., Bujacz G., Guga P., Thermal Stability and Conformation of Antiparallel Duplexes Formed by P-Stereodefined Phosphorothioate DNA/LNA Chimeric Oligomers with DNA and RNA Matrices, Org. Biomol. Chem., 2015, 13, 10032–10040
https://pubs.rsc.org/en/content/articlelanding/2015/ob/c5ob01474c
Jasiński M., Gerding J.S., Jankowiak A., Gębicki K., Romański J., Jastrzębska K., Sivaramamoorthy A., Mason K., Evans D.H., Celeda M., Kaszyński P., Functional Group Transformations in Derivatives of 6-Oxoverdazyl, J. Org. Chem., 2013, 78, 7445-7454
https://pubs.acs.org/doi/10.1021/jo400843y
Patents:
WO/2021/155120 (USA): Dumbović G. (CRO/US), Krishna H. (IN/US), Jastrzebska K. (PL/US), Caruthers M. (US), Rinn J.L. (US), Method for retaining splicing RNAs in the nucleus based on chemically modified antisense Oligonucleotides
WO/2019/060522 (USA): Krishna H. (IN/US), Jastrzebska K. (PL/US), Caruthers M. (US), Paul S. (US), Veedu R.N. (AU), Thiomorpholino oligonucleotides for the treatment of muscular dystrophy
