CeNT
herb

Laboratory of Bioorganic Chemistry

Laboratory of Bioorganic Chemistry is focused on the synthesis, properties and applications of modified nucleotides (including analogs of mRNA 5’ cap, nucleoside triphosphates, nucleotide sugars, nucleoside phosphosulfates and many others). The main goal of our research is to create tools useful for elucidating biological processes involving nucleotides and to find new potential nucleotide-derived therapeutics.

To do so, we develop new synthetic methods for the chemical and enzymatic synthesis of nucleotides and their analogs. We are particularly interested in the synthesis and properties of nucleotides modified within the phosphate moieties. We design nucleotide analogs that increase cellular stability of mRNA and nucleotide-derived inhibitors of protein biosynthesis with increased stability under cellular conditions. We synthesize fluorescently labeled nucleotides, nucleotides with affinity tags as well as nucleotide-probes for NMR and EPR experiments. We also prepare and evaluate conjugates of nucleotides with nano(bio)materials.

The laboratory operates in two locations – team uses the hospitality of the Department of Biophysics, Faculty of Physics, University of Warsaw.

Prof. Jacek Jemielity
email: j.jemielity@cent.uw.edu.pl
phone: +48 22 55 43774
room: 06.44
ResearchGate: https://www.researchgate.net/profile/Jacek_Jemielity


Kinetic analysis of IFIT1 and IFIT5 interactions with different native and engineered RNAs and its consequences for designing mRNA-based therapeutics
Miedziak, B., Dobieżyńska, A., Darżynkiewicz, Z. M., Bartkowska, J., Miszkiewicz, J., Kowalska, J., ... & Darzynkiewicz, E.
RNA, 26(1), 58-68.
Purine and pyrimidine dinucleoside polyphosphates differentially affect the phenylpropanoid pathway in Vitis vinifera L. cv. Monastrell suspension cultured cells.
Pietrowska-Borek, M., Wojdyła-Mamoń, A., Dobrogojski, J., Młynarska-Cieślak, A., Baranowski, M. R., Dąbrowski, J. M., ... & Guranowski, A.
Plant Physiology and Biochemistry, 147, 125-132.
Phosphodiester modifications in mRNA polyA tail prevent deadenylation without compromising protein expression
Strzelecka, D., Smietanski, M., Sikorski, P. J., Warminski, M., Kowalska, J., & Jemielity, J.
RNA, 26(12), 1815-1837
Synthesis of trifluoromethylated purine ribonucleotides and their evaluation as 19F NMR probes
Chrominski, M., Baranowski, M. R., Chmielinski, S., Kowalska, J., & Jemielity, J.
The Journal of organic chemistry, 85(5), 3440-3453
Direct High-Throughput Screening Assay for mRNA Cap Guanine-N7 Methyltransferase Activity
Kasprzyk, R., Fido, M., Mamot, A., Wanat, P., Smietanski, M., Kopcial, M., ... & Jemielity, J.
Chemistry (Weinheim an der Bergstrasse, Germany)
Exploring tryptamine conjugates as pronucleotides of phosphate-modified 7-methylguanine nucleotides targeting cap-dependent translation
Golojuch, S., Kopcial, M., Strzelecka, D., Kasprzyk, R., Baran, N., Sikorski, P. J., ... & Jemielity, J.
Bioorganic & medicinal chemistry, 28(13), 115523
5′-fluoro(di)phosphate-labeled oligonucleotides are versatile molecular probes for studying nucleic acid secondary structure and interactions by 19F NMR
Baranowski, M. R., Warminski, M., Jemielity, J., & Kowalska, J.
Nucleic acids research, 48(15), 8209-8224
Efficient Synthesis of Trifluoromethylated Purine Ribonucleosides and Ribonucleotides
Chrominski, M., Kowalska, J., & Jemielity, J.
Current Protocols in Nucleic Acid Chemistry, 83(1), e118
Solid-Phase Synthesis of RNA 5′-Azides and Their Application for Labeling, Ligation, and Cyclization Via Click Chemistry
Warminski, M., Kowalska, J., & Jemielity, J.
Current Protocols in Nucleic Acid Chemistry, 82(1), e112
The identity and methylation status of the first transcribed nucleotide in eukaryotic mRNA 5′ cap modulates protein expression in living cells
Sikorski, P. J., Warminski, M., Kubacka, D., Ratajczak, T., Nowis, D., Kowalska, J., & Jemielity, J.
Nucleic acids research, 48(4), 1607-1626
Fluorescent Turn‐On Probes for the Development of Binding and Hydrolytic Activity Assays for MRNA Cap‐Recognizing Proteins
Kasprzyk. R., Starek B.J., Ciechanowicz, S., Kubacka D., Kowalska J., Jemielity J. (2019).
Chemistry – A European Journal, vol. 25, no. 27, 2019, pp. 6646–6646.
N1-Propargylguanosine Modified mRNA Cap Analogs: Synthesis, Reactivity, and Applications to the Study of Cap-Binding Proteins
Kopcial, M., Wojtczak, B. A., Kasprzyk, R., Kowalska, J., & Jemielity, J. (2019).
Molecules, 24(10), 1899.
7-Methylguanosine monophosphate analogues with 5′-(1,2,3-triazoyl) moiety: Synthesis and evaluation as the inhibitors of cNIIIB nucleotidase
Kozarski, M., Kubacka, D., Wojtczak, B. A., Kasprzyk, R., Baranowski, M. R., & Kowalska, J. (2018).
Bioorganic & medicinal chemistry, 26(1), 191-199.
Structure of the activated Edc1-Dcp1-Dcp2-Edc3 mRNA decapping complex with substrate analog poised for catalysis
Mugridge, J. S., Tibble, R. W., Ziemniak, M., Jemielity, J., & Gross, J. D. (2018).
Nature communications, 9(1), 1152
Roquin targets mRNAs in a 3′-UTR-specific manner by different modes of regulation
Essig, K., Kronbeck, N., Guimaraes, J. C., Lohs, C., Schlundt, A., Hoffmann, A., ... & Jemielity, J. (2018).
Nature communications, 9
Exploring the potential of phosphotriazole 5′ mRNA cap analogues as efficient translation initiators
Walczak, S., Sikorski, P. J., Kasprzyk, R., Kowalska, J., & Jemielity, J. (2018).
Organic & biomolecular chemistry, 16(36), 6741-6748
5′-Phosphorothiolate Dinucleotide Cap Analogues: Reagents for Messenger RNA Modification and Potent Small-Molecular Inhibitors of Decapping Enzymes
Wojtczak, B. A., Sikorski, P. J., Fac-Dabrowska, K., Nowicka, A., Warminski, M., Kubacka, D., ... & Jemielity, J. (2018).
Journal of the American Chemical Society, 140(18), 5987-5999
ExciTides: NTP-derived probes for monitoring pyrophosphatase activity based on excimer-to-monomer transitions
Wanat, P., Kasprzyk, R., Kopcial, M., Sikorski, P. J., Strzelecka, D., Jemielity, J., & Kowalska, J. (2018).
Chemical Communications, 54(70), 9773-9776
mRNAs biotinylated within the 50 cap and protected against decapping: new tools to capture RNA – protein complexes
Bednarek, S., Madan, V., Sikorski, P. J., Bartenschlage, R., Kowalska, J., & Jemielity, J. (2018).
Philosophical Transactions of The Royal Society B, 373
Nicotinamide-Containing Di- and Trinucleotides as Chemical Tools for Studies of NAD-Capped RNAs
Mlynarska-Cieslak, A., Depaix, A., Grudzien-Nogalska, E., Sikorski, P. J., Warminski, M., Kiledjian, M., ... & Kowalska, J. (2018).
Organic letters.
5′-Phosphorothiolate Dinucleotide Cap Analogues: Reagents for Messenger RNA Modification and Potent Small-Molecular Inhibitors of Decapping Enzymes
Wojtczak, B. A., Sikorski, P. J., Fac-Dabrowska, K., Nowicka, A., Warminski, M., Kubacka, D., . . .& Jemielity, J.
Journal of the American Chemical Society, 140(18)
mRNAs biotinylated within the 5′ cap and protected against decapping: new tools to capture RNA–protein complexes
Bednarek, S., Madan, V., Sikorski, P. J., Bartenschlager, R., Kowalska, J., & Jemielity, J.
Philosophical Transactions of the Royal Society B: Biological Sciences, 373(1762), 20180167
Analysis of mononucleotides by tandem mass spectrometry: investigation of fragmentation pathways for phosphate- and ribose-modified nucleotide analogues
Strzelecka, D., Chmielinski, S., Bednarek, S., Jemielity, J., & Kowalska, J. (2017).
Scientific reports, 7(1), 8931.
Applications of Phosphate Modification and Labeling to Study (m) RNA Caps
Warminski, M., Sikorski, P. J., Kowalska, J., & Jemielity, J. (2017).
Topics in Current Chemistry, 375(1), 16.
Central Regulatory Role for SIN1 in Interferon γ (IFNγ) Signaling and Generation of Biological Responses
Kroczynska, B., Blyth, G. T., Rafidi, R. L., Majchrzak-Kita, B., Xu, L., Saleiro, D., Kosciuczuk, E.M., Jemielity, J., Su, B., Altman, J.K. & Eklund, E. A. (2017).
Journal of Biological Chemistry, 292(11), 4743-4752.
eIF4E phosphorylation by MST1 reduces translation of a subset of mRNAs, but increases lncRNA translation
Min, K. W., Davila, S., Zealy, R. W., Lloyd, L. T., Lee, I. Y., Lee, R., Roh, K.H., Jung, A., Jemielity, J., Choi, E.J. & Chang, J. H. (2017).
Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms, 1860(7), 761-772.
Amino-Functionalized 5′ Cap Analogs as Tools for Site-Specific Sequence-Independent Labeling of mRNA
Warminski, M., Sikorski, P. J., Warminska, Z., Lukaszewicz, M., Kropiwnicka, A., Zuberek, J., Darzynkiewicz, E., Kowalska, J. Darzynkiewicz, E., Kowalska, J. & Jemielity, J. (2017).
ioconjugate chemistry, 28(7), pp.1978-1992.
Synthesis of RNA 5′-Azides from 2′-O-Pivaloyloxymethyl-Protected RNAs and Their Reactivity in Azide–Alkyne Cycloaddition Reactions
Warminski, M., Kowalska, J., & Jemielity, J. (2017).
Organic letters, 19(13), 3624-3627.
mRNA cap analogues substituted in the tetraphosphate chain with CX2: identification of O-to-CCl2 as the first bridging modification that confers resistance to decapping without impairing translation
Rydzik, A. M., Warminski, M., Sikorski, P. J., Baranowski, M. R., Walczak, S., Kowalska, J., Zuberek, J., Lukaszewicz, M., Nowak, E., W. Claridge, T.D. & Darzynkiewicz, E. (2017).
Nucleic acids research, 45(15), 8661-8675.
Synthesis of Aminoglycoside-2′-O-Methyl Oligoribonucleotide Fusions.
Granqvist, L., Kraszewski, A., Tähtinen, V., & Virta, P. (2017).
Molecules, 22(5), 760.
Comparison of preribosomal RNA processing pathways in yeast, plant and human cells – focus on coordinated action of endo- and exoribonucleases
Tomecki, R., Sikorski, P. J., & Zakrzewska‐Placzek, M. (2017).
FEBS letters, 591(13), 1801-1850.
On the Interactions of Fused Pyrazole Derivative with Selected Amino Acids: DFT Calculations
Czaja, K., Kujawski, J., Jodłowska-Siewert, E., Szulc, P., Ratajczak, T., Krygier, D., ... & Bernard, M. K. (2017).
Journal of Chemistry, 2017.
Structural and spectroscopic properties of itraconazole and ketoconazole–Experimental and theoretical studies
Kujawski, J., Czaja, K., Jodłowska-Siewert, E., Dettlaff, K., Żwawiak, J., Kujawski, R., Ratajczak, T. & Bernard, M. K. (2017).
Journal of Molecular Structure, 1146, 259-266.
Azido-Functionalized 5ʹ-Cap Analogs for Preparation of Translationally Active mRNAs Suitable for Fluorescent Labeling in Living Cells
Mamot, A.; Sikorski, P.; Warminski, M.; Kowalska, J.; Jemielity, J., (2017).
Angewandte Chemie International Edition, 56(49):15628-15632
Cap analogs modified with 1, 2-dithiodiphosphate moiety protect mRNA from decapping and enhance its translational potential.
trenkowska, M., Grzela, R., Majewski, M., Wnek, K., Kowalska, J., Lukaszewicz, M., ... & Jemielity, J. (2016).
Nucleic acids research, 44(20), 9578-9590.
Structural basis of mRNA-cap recognition by Dcp1-Dcp2.
Mugridge, J. S., Ziemniak, M., Jemielity, J., & Gross, J. D. (2016).
Nature Structural and Molecular Biology, 23(11), 987.
Synthetic m 3 G-CAP attachment necessitates a minimum trinucleotide constituent to be recognised as a nuclear import signal.
Honcharenko, M., Bestas, B., Jezowska, M., Wojtczak, B. A., Moreno, P. M. D., Romanowska, J., Darzynkiewicz E., Jemielity J., ... & Strömberg, R. (2016).
RSC Advances, 6(56), 51367-51373.
Acetylpyrene-labelled 7-methylguanine nucleotides: unusual fluorescence properties and application to decapping scavenger activity monitoring.
Kasprzyk, R., Kowalska, J., Wieczorek, Z., Szabelski, M., Stolarski, R., & Jemielity, J. (2016).
Organic & biomolecular chemistry, 14(16), 3863-3868.
Fluorescent HTS assay for phosphohydrolases based on nucleoside 5ʹ-fluorophosphates: application in screening for inhibitors of mRNA Decapping Scavenger and PDE-I
Baranowski, M. R., Nowicka, A., Jemielity, J., & Kowalska, J. (2016)
Organic & biomolecular chemistry, 14(20), 4595-4604
Clickable trimethylguanosine cap analogs modified within the triphosphate bridge: synthesis, conjugation to RNA and susceptibility to degradation
Wojtczak, B. A., Warminski, M., Kowalska, J., Lukaszewicz, M., Honcharenko, M., Smith, C. E., ... & Jemielity, J. (2016)
RSC Advances, 6(10), 8317-8328
Two-headed tetraphosphate cap analogs are inhibitors of the Dcp1/2 RNA decapping complex
Ziemniak, M., Mugridge, J. S., Kowalska, J., Rhoads, R. E., Gross, J. D., & Jemielity, J. (2016)
RNA, 22(4), 518-529
Interferon γ (IFNγ)-Signaling via mTORC2 and Regulatory Effects in the Generation of Type II IFN Biological Responses
Kroczynska, B., Rafidi, R. L., Majchrzak-Kita, B., Kosciuczuk, E. M., Blyth, G. T., Jemielity, J., ... & Fish, E. N. (2016)
Journal of Biological Chemistry, jbc-M115
Synthetic Capped mRNAs for Cap-Specific Photo-Cross-Linking Experiments
Kowalska, J., Martin, F., & Jemielity, J. (2016).
Synthetic mRNA: Production, Introduction Into Cells, and Physiological Consequences, 31-43.
Kinetic and solvent isotope effects on biotransformation of aromatic amino acids and their derivatives
Kańska, M., Jemielity, J., Pająk, M., Pałka, K., Podsadni, K., & Winnicka, E. (2016)
Journal of Labelled Compounds and Radiopharmaceuticals, 59(14), 627-634.
Phosphate-modified analogues of m7GTP and m7Gppppm7G – synthesis and biochemical properties
Ziemniak, M., Kowalska, J., Lukaszewicz, M., Zuberek, J., Wnek, K., Darzynkiewicz, E., & Jemielity, J. (2015)
Bioorganic & medicinal chemistry, 23(17), 5369-5381
Synthesis of fluorophosphate nucleotide analogues and their characterization as tools for 19F NMR studies.
Baranowski, M. R., Nowicka, A., Rydzik, A. M., Warminski, M., Kasprzyk, R., Wojtczak, B. A., ... & Jemielity, J. (2015).
The Journal of organic chemistry 80, no. 8 (2015): 3982-3997
Ethynyl, 2-propynyl, and 3-butynyl C-phosphonate analogues of nucleoside di-and triphosphates: synthesis and reactivity in CuAAC.
Wanat, P., Walczak, S., Wojtczak, B. A., Nowakowska, M., Jemielity, J., & Kowalska, J. (2015).
Organic letters, 17(12), 3062-3065.
Gold-decorated polymer vessel structures as carriers of mRNA cap analogues
Kijewska, K., Głowala, P., Kowalska, J., Jemielity, J., Kaczyńska, K., Janiszewska, K., ... & Wiktorska, K. (2015)
Polymer, 57, 77-87
Virus-like particle-mediated intracellular delivery of mRNA cap analog with in vivo activity against hepatocellular carcinoma.
Zochowska, M., Piguet, A. C., Jemielity, J., Kowalska, J., Szolajska, E., Dufour, J. F., & Chroboczek, J. (2015).
Nanotechnology, Biology and Medicine, 11(1), 67-76.
Synthesis of fluorophosphates nucleotide analogues and their characterization as tools for 19F NMR studies
Baranowski, M. R., Nowicka, A., Rydzik, A. M., Warminski, M., Kasprzyk, R., Wojtczak, B. A., ... & Jemielity, J. (2015)
The Journal of organic chemistry, 80(8), 3982-3997.
Cap analogs containing 6-thioguanosine–reagents for the synthesis of mRNAs selectively photo-crosslinkable with cap-binding biomolecules.
Nowakowska, M., Kowalska, J., Martin, F., d'Orchymont, A., Zuberek, J., Lukaszewicz, M., ... & Jemielity, J. (2014).
Organic & biomolecular chemistry, 12(27), 4841-4847.
Cap analogs containing 6-thioguanosine – reagents for the synthesis of mRNAs selectively photo-crosslinkable with cap-binding biomolecules
Nowakowska, M., Kowalska, J., Martin, F., d'Orchymont, A., Zuberek, J., Lukaszewicz, M., ... & Jemielity, J. (2014).
Organic & biomolecular chemistry, 12(27), 4841-4847.
Synthesis, properities and biological activity of boranophosphate analogs of the mRNA cap: versalite tools for manipulation of therapeutically relevant cap-dependent processes
Kowalska, J., Wypijewska del Nogal, A., Darzynkiewicz, Z. M., Buck, J., Nicola, C., Kuhn, A. N., ... & Maciejczyk, M. (2014)
Nucleic acids research, 42(16), 10245-10264
Analysis of decapping scavenger cap complex using modified cap analogs reveals molecular determinants for efficient cap binding.
Wypijewska del Nogal, A., Surleac, M. D., Kowalska, J., Lukaszewicz, M., Jemielity, J., Bisaillon, M., ... & Bojarska, E. (2013).
The FEBS journal, 280(24), 6508-6527.
Hint2, the mitochondrial nucleoside 5’-phosphoramidate hydrolase; properties of the homogeneous protein from sheep (Ovis aries) liver.
Wypijewska del Nogal, A., Surleac, M. D., Kowalska, J., Lukaszewicz, M., Jemielity, J., Bisaillon, M., ... & Bojarska, E. (2013).
The FEBS journal, 280(24), 6508-6527.
The synthesis of isopropylidene mRNA cap analogs modified with phosphorothioate moiety and their evaluation as promoters of mRNA translation.
Warminski, M., Kowalska, J., Buck, J., Zuberek, J., Lukaszewicz, M., Nicola, C., ... & Jemielity, J. (2013).
Bioorganic & medicinal chemistry letters, 23(13), 3753-3758.
Magnetic-nanoparticle-decorated polypyrrole microvessels: Toward encapsulation of mRNA cap analogues.
Kijewska, K., Jarzębińska, A., Kowalska, J., Jemielity, J., Kępińska, D., Szczytko, J., ... & Twardowski, A. (2013).
Biomacromolecules, 14(6), 1867-1876.
Potential therapeutic applications of RNA cap analogs
Ziemniak, M., Strenkowska, M., Kowalska, J., & Jemielity, J. (2013)
Future medicinal chemistry, 5(10), 1141-1172.

Laboratory of Bioorganic Chemistry operates in two locations – team uses the hospitality of the Department of Biophysics, Faculty of Physics, University of Warsaw. CeNT team cooperates with employees of the Faculty of Physics:

Anais Depaix, PhD

Karolina Kaczmarska, Msc

Joanna Kowalska, PhD

Dorota Kubacka, PhD

Michał Magda, Msc

Tomasz Śpiewla, Msc