Laboratorium Chemii Bioorganicznej

W Laboratorium Chemii Bioorganicznej prowadzone są badania nad syntezą, właściwościami i zastosowaniami modyfikowanych nukleotydów (analogów końca 5’ mRNA – kapu, trifosforanów nukleozydów, nukleotydocukrów, fosfosiarczanów nukleozydów i innych).

Głównym celem naszych badań jest tworzenie narzędzi do poznawania i zgłębiania procesów biologicznych, w które nukleotydy są zaangażowane, jak również poszukiwanie nowych czynników terapeutycznych opartych na strukturze nukleotydów i kwasów nukleinowych. Opracowujemy nowe metody syntezy chemicznej i enzymatycznej nukleotydów i ich analogów. Prowadzimy badania nad syntezą i właściwościami nukleotydów modyfikowanych na różne sposoby w obrębie reszty fosforanowej. Projektujemy analogi nukleotydów, zwiększające stabilność mRNA oraz trwałe w warunkach komórkowych inhibitory biosyntezy białka. Syntetyzujemy nukleotydy znakowane fluorescencyjnie, nukleotydy zawierające znaczniki powinowactwa, nukleotydowe sondy NMR i EPR. Tworzymy i badamy koniugaty nukleotydów z nano(bio)materiałami.

Laboratorium funkcjonuje w dwóch lokalizacjach- zespół korzysta z gościnności Zakładu Biofizyki IFD, Wydziału Fizyki UW.

dr hab. Jacek Jemielity , Prof. UW
e-mail: j.jemielity@cent.uw.edu.pl
telefon: +48 22 55 43774
pokój: 06.44


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.
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
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
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
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
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.
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.
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.
Min, K. W., Davila, S., Zealy, R. W., Lloyd, L. T., Lee, I. Y., Lee, R., … & Chang, J. H. (2017). 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.
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 2017, 591(13), 1801–1850, IF=3.623
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.
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.
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.
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
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.
Cap analogs modified with 1,2-dithiodiphosphate moiety protect mRNA from decapping and enhance its translational potential
Strenkowska, M., Grzela, R., Majewski, M., Wnek, K., Kowalska, J., Lukaszewicz, M., ... & Jemielity, J. (2016).
Nucleic acids research, 44(20), 9578-9590
A novel route for preparing 5′ cap mimics and capped RNAs: phosphate-modified cap analogues obtained via click chemistry
Walczak, S., Nowicka, A., Kubacka, D., Fac, K., Wanat, P., Mroczek, S., ... & Jemielity, J.
Chemical Science, 8(1), 260-267
Structural basis of mRNA-cap recognition by Dcp1–Dcp2
Mugridge, J. S., Ziemniak, M., Jemielity, J., & Gross, J. D.
Nature structural & molecular biology
Cap analogs modified with 1, 2-dithiodiphosphate moiety protect mRNA from decapping and enhance its translational potential.
Strenkowska, 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.
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, no. 16 (2016): 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 m3G-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., ... & Strömberg, R. (2016).
RSC Advances, 6(56), 51367-51373.
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(8), 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).
Nanomedicine: Nanotechnology, Biology and Medicine 11, no. 1 (2015): 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.