Projects funded by the NCN

Information on the principal investigator and host institution

Information of the project and the call

Keywords

Equipment

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Designing mRNA transcripts resistant to enzymatic cap hydrolysis applicable for anti-cancer vaccines; multiplexed biochemical and biophysical studies on representative classes of decapping enzymes.

2013/08/A/NZ1/00866

Keywords:

5' mRNA monomethylguanosine cap trimethylguanosine cap cap-4 decapping enzymes HIT hydrolases NUDIX hydrolases human DcpS yeast Dcs1 C.elegans DcpS Nudt16 yeast Dcp2/Dcp1 Trypanosomatide HIT-45 translation initiation factor eIF4E fluorescence titration TST Reverse Phase HPLC isothermal calorimetric titration ITC near UV circular dichroism CD stopped flow kinetic and thermodynamic parameters molecular modeling NMR spectroscopy mass spectroscopy non-hydrolyzable synthetic cap analogues anti-tumor mRNA vaccinies anti reverse cap analogues ARCAs phosphate bridge modifications alternatively capped oligonucleotides and mRNAs chemoenzymatic mRNA capping protein translation translation inhibition

Descriptors:

  • NZ1_1: Molecular biology
  • NZ1_3: Biophysics
  • NZ1_6: Synthetic biology

Panel:

NZ1 - Molecular biology, structural biology, biotechnology: molecular biology, structural biology, biotechnology

Host institution :

Uniwersytet Warszawski, Centrum Nowych Technologii

woj. mazowieckie

Other projects carried out by the institution 

Principal investigator (from the host institution):

prof. Edward Darżynkiewicz 

Number of co-investigators in the project: 20

Call: MAESTRO 4 - announced on 2012-12-15

Amount awarded: 2 983 800 PLN

Project start date (Y-m-d): 2013-09-23

Project end date (Y-m-d): 2019-09-22

Project duration:: 72 months (the same as in the proposal)

Project status: Project settled

Equipment purchased [PL]

  1. Komputery.
  2. Pipeta 8-kanałowa o zmiennych pojemnościach z pudełkami na końcówki (2 484 PLN)
  3. Spektrofotometr dwuwiązkowy UV-VIS.
  4. Wymienny termoblok na probówki stożkowe (2 329 PLN)
  5. Wyparka próżniowa.
  6. Komputery, oprogramowanie biurowe i specjalistyczne oraz akcesoria komputerowe (7 226 PLN)
  7. Luminometr (38 000 PLN)
  8. Aparat do badania oddziaływań pomiędzy makrocząsteczkami.
  9. Chłodziarko-zamrażarki.
  10. Kolektor frakcji (32 000 PLN)
  11. Koszyki do wirowania płytek (7 131 PLN)
  12. Spektrofluorymetr (220 000 PLN)
  13. Aparat HPLC (190 000 PLN)
  14. Podręczny mikrofalowy autoklaw.
  15. Witryna chłodnicza.
  16. Wózki do pożywek.

Information in the final report

  • Publication in academic press/journals (19)
  • Book publications / chapters in book publications (1)
  1. Amino-Functionalized 5' Cap Analogs as Tools for Site-Specific Sequence-Independent Labeling of mRNA
    Authors:
    Warminski M., Sikorski P.J., Warminska Z., Lukaszewicz M., Kropiwnicka A., Zuberek J., Darzynkiewicz E., Kowalska J., Jemielity J.
    Academic press:
    Bioconjugate Chemistry (rok: 2017, tom: 28, strony: 1978-1992), Wydawca: American Chemical Society
    Status:
    Published
    DOI:
    10.1021/acs.bioconjchem.7b00291 - link to the publication
  2. Cap analogs containing 6-thioguanosine - reagents for the synthesis of mRNAs selectively photo-crosslinkable with cap-binding biomolecules
    Authors:
    Nowakowska M., Kowalska J., Martin F., d'Orchymont A., Zuberek J., Lukaszewicz M., Darzynkiewicz E., Jemielity J.
    Academic press:
    Organic & Biomolecular Chemistry (rok: 2014, tom: 12, strony: 4841-4847), Wydawca: Royal Society of Chemistry
    Status:
    Published
    DOI:
    10.1039/c4ob00059e - link to the publication
  3. Decapping Scavenger (DcpS) enzyme: Advences in its structure, activity and roles in the cap-dependent mRNA metabolism
    Authors:
    Milac A.L., Bojarska E., Wypijewska del Nogal A.
    Academic press:
    Biochimica at Biophysica Acta - Gene Regulatory Mechanism (rok: 2014, tom: 1839, strony: 452-462), Wydawca: Elsevier
    Status:
    Published
    DOI:
    10.1016/j.bbagrm.2014.04.007 - link to the publication
  4. Decapping Scavenger Enzyme Activity toward N2-substituted 5' end mRNA Cap Analogues
    Authors:
    Pietrow P., Ferenc-Mrozek A., Piecyk K., Bojarska E., Darzynkiewicz E., Jankowska-Anyszka M.
    Academic press:
    ACS Omega (rok: 2019, tom: 4, strony: 17576-17580), Wydawca: ACS Publications
    Status:
    Published
    DOI:
    10.1021/acsomega.9b02715 - link to the publication
  5. Effect of different N7 substitution of dinucleotide cap analogs on the hydrolytic susceptibility towards scavenger decapping enzymes (DcpS)
    Authors:
    Piecyk K., Darzynkiewicz Z.M., Jankowska-Anyszka M., Ferenc-Mrozek A., Stepinski J., Darzynkiewicz E., Bojarska E.
    Academic press:
    Biochemical and Biophysical Research Communications (rok: 2015, tom: 464, strony: 89-93), Wydawca: Elsevier
    Status:
    Published
    DOI:
    10.1016/j.bbrc.2015.06.001 - link to the publication
  6. Kinetic analysis of IFIT1 and IFIT5 interaction with different native and engineered RNAs and its consequences for designing mRNA-based therapeutics.
    Authors:
    Miedziak B., Dobiezynska A., Darzynkiewicz Z.M., Bartkowska J., Miszkiewicz J., Kowalska J., Warminski M., Tyras M., Trylska J., Jemielity J., Darzynkiewicz E., Grzela R.
    Academic press:
    RNA (rok: 2020, tom: 26, strony: 58-68), Wydawca: Cold Spring Harbor Laboratory Press
    Status:
    Published
    DOI:
    10.1261/rna/073304.119 - link to the publication
  7. Modified ARCA analogs providing enhanced translational properties of capped mRNAs
    Authors:
    Kocmik I., Piecyk K., Rudzinska M., Niedzwiecka A., Darzynkiewicz E., Grzela R., Jankowska-Anyszka M.
    Academic press:
    Cell Cycle (rok: 2018, tom: 17, strony: 1624-1636), Wydawca: Taylor & Francis
    Status:
    Published
    DOI:
    10.1080/15384101.2018.1486164 - link to the publication
  8. Molecular recognition of mRNA 5' cap by 3' poly(A)-specific ribonuclease (PARN) differs from interactions known for other cap-binding proteins
    Authors:
    Niedzwiecka A., Nilsson P., Worch R., Stepinski J., Darzynkiewicz E., Virtanen A.
    Academic press:
    Biochimica at Biophysica Acta - Proteins and Proteomics (rok: 2016, tom: 1864, strony: 331-345), Wydawca: Elsevier
    Status:
    Published
    DOI:
    10.1016/j.bbapap.2016.01.002 - link to the publication
  9. Phosphate-modified analogues of m7GTP and m7Gppppm7G - Synthesis and biochemical properties
    Authors:
    Ziemniak M., Kowalska J., Lukaszewicz M., Zuberek J., Wnek K., Darzynkiewicz E., Jemielity J.
    Academic press:
    Bioorganic & Medicinal Chemistry (rok: 2015, tom: 23, strony: 5369-5381), Wydawca: Elsevier
    Status:
    Published
    DOI:
    10.1016/j.bmc.2015.07.052 - link to the publication
  10. Quantum dots use both LUMO and surface trap electrons in photoreduction process
    Authors:
    Darzynkiewicz Z.M., Pedziwiatr M., Grzyb J.
    Academic press:
    Journal of Luminescence (rok: 2017, tom: 183, strony: 401-409), Wydawca: Elsevier
    Status:
    Published
    DOI:
    10.1016/j.jlumin.2016.11.070 - link to the publication
  11. Cap analgs modified with 1,2-dithiodiphosphate moiety protect mRNA from decapping and enhance its translational potential
    Authors:
    Strenkowska M., Grzela R., Majewski M., Wnek K., Kowalska J., Lukaszewicz M., Zuberek J., Darzynkiewicz E., Kuhn A.N., Sahin U., Jemielity J.
    Academic press:
    Nucleic Acids Research (rok: 2016, tom: 44, strony: 9578-9590), Wydawca: Oxford University Press
    Status:
    Published
    DOI:
    10.1093/nar/gkw896 - link to the publication
  12. Hydrolytic activity of human Nudt16 enzyme on dinucleotide cap analogs and short capped oligonucleotides
    Authors:
    Grzela R., Nasilowska K., Lukaszewicz M., Tyras M., Stepinski J., Jankowska-Anyszka M., Bojarska E., Darzynkiewicz E.
    Academic press:
    RNA (rok: 2018, tom: 24, strony: 633-642), Wydawca: Cold Spring Harbor Laboratory Press
    Status:
    Published
    DOI:
    10.1261/rna.065698.118 - link to the publication
  13. Synthesis, properties, and biological activity of boranophosphate analogs of the mRNA cap: versalite tools for manipulation of therapeutically relevant cap-dependent processes
    Authors:
    Kowalska J., Wypijewska del Nogal A., Darzynkiewicz Z.M., Buck J., Nicola C., Kuhn A.N., Lukaszewicz M., Zuberek J., Strenkowska M., Ziemniak M., Maciejczyk M., Bojarska E., Rhoads R.E., Darzynkiewicz E., Sahin U., Jemielity J.
    Academic press:
    Nucleic Acids Research (rok: 2014, tom: 42, strony: 10245-10264), Wydawca: Oxford University Press
    Status:
    Published
    DOI:
    10.1093/nar/gku757 - link to the publication
  14. Clickable trimethylguanosine cap analogs modified within the triphosphate bridge: synthesis, conjugation to RNA and susceptibility to degradation
    Authors:
    Wojtczak B.A., Warminski M., Kowalska J., Lukaszewicz M., Honcharenko M., Smith C.I.E., Stromberg R., Darzynkiewicz E., Jemielity J.
    Academic press:
    RCS Advances (rok: 2016, tom: 6, strony: 8317-8328), Wydawca: Royal Society of Chemistry
    Status:
    Published
    DOI:
    10.1039/c5ra25684d - link to the publication
  15. Effect of the His-Tag Location on Decapping Scavenger Enzymes and Their Hydrolytic Activity toward Cap Analogs
    Authors:
    Ferenc-Mrozek A., Bojarska E., Stepinski J., Darzynkiewicz E., Lukasiewicz M.
    Academic press:
    ACS Omega (rok: 2020, tom: 5, strony: 10759-10766), Wydawca: ACS Publications
    Status:
    Published
    DOI:
    10.1021/acsomega.0c00304 - link to the publication
  16. Helix 69 of Escherichia coli 23S ribosomal RNA as a peptide nucleic acid target
    Authors:
    Kulik M., Markowska-Zagrajek A., Wojciechowska M., Grzela R., Witula T., Trylska J.
    Academic press:
    Biochimie (rok: 2017, tom: 138, strony: 32-42), Wydawca: Elsevier
    Status:
    Published
    DOI:
    10.1016/j.biochi.2017.04.001 - link to the publication
  17. Structural analysis of human 2'-O-ribose methyltransferases involved in mRNA cap structure formation
    Authors:
    Smietanski M., Werner M., Purta E., Kaminska K.H., Stepinski J., Darzynkiewicz E., Nowotny M., Bujnicki J.M.
    Academic press:
    Nature Communications (rok: 2014, tom: 5, strony: 45301), Wydawca: Macmillan Publishers Limited
    Status:
    Published
    DOI:
    10.1038/ncomms4004 - link to the publication
  18. Triazole-containing monophosphate mRNA cap analogs as effective translation inhibitors
    Authors:
    Piecyk K., Lukaszewicz M., Darzynkiewicz E., Jankowska-Anyszka M.
    Academic press:
    RNA (rok: 2014, tom: 20, strony: 1539-1547), Wydawca: Cold Spring Harbor Laboratory Press
    Status:
    Published
    DOI:
    10.1261/rna.046193.114 - link to the publication
  19. eIF4E-like complexes formed by cap-binding homolog TbEIF4E5 with TbEIF4G1 or TbEIF4G2 are implicated in post-transcriptional regulation in Trypanosoma brucei
    Authors:
    Freire E.R., Vashisht A.A., Malvezzi A.M., Zuberek J., Langousis G., Saada E.A., Nascimento J. DE F., Stepinski J., Darzynkiewicz E., Hill K., De Melo Neto O.P., Wohlschlegel J.A., Sturm N.R., Campbell D.A.
    Academic press:
    RNA (rok: 2014, tom: 20, strony: 1272-1286), Wydawca: Cold Spring Harbor Laboratory Press
    Status:
    Published
    DOI:
    10.1261/rna.045534.114 - link to the publication
  1. mRNA and snRNA Cap Analogs: Synthesis and Applications
    Authors:
    Stepinski J., Darzynkiewicz E.
    Book:
    Chemical Biology of Nucleic Acids - Fundamentals and Clinical Applications, RNA Technologies (rok: 2014, tom: 28, strony: 511-561), Wydawca: Springer-Verlag
    Status:
    Published

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