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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Transient protein states in designing small-molecule inhibitors of protein-protein interactions

2014/12/W/NZ1/00457

Keywords:

NMR chemical probes small-molecules proteins cancer

Descriptors:

  • NZ1_3: Biophysics
  • NZ1_4: Structural biology
  • NZ1_1: Molecular biology

Panel:

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

Host institution :

Uniwersytet Jagielloński, Wydział Chemii

woj. małopolskie

Other projects carried out by the institution 

Principal investigator (from the host institution):

prof. Tadeusz Holak 

Number of co-investigators in the project: 17

Call: SYMFONIA 2

Amount awarded: 6 996 600 PLN

Project start date (Y-m-d): 2014-12-15

Project end date (Y-m-d): 2020-12-14

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

Project status: Project settled

Equipment purchased [PL]

  1. Amicon system (2 szt.) (12 300 PLN)
  2. Chromatograf typu "Flash" (300 000 PLN)
  3. Mieszadło "Vortex" (3 000 PLN)
  4. Mikroskop laboratoryjny.
  5. Windows 10.
  6. Zestaw chromatograficzny FPLC (80 000 PLN)
  7. Aparat do elektroforezy DNA (2 747 PLN)
  8. Inkubator CO2.
  9. Kolumna chromatograficzna Superdex (9 675 PLN)
  10. Mieszadło magnetyczne z płytą grzewczą i kontrolą temperatury.
  11. Transiluminator (światło białe) (2 460 PLN)
  12. Pompa próżniowa (2 szt.) (60 000 PLN)
  13. Waga laboratoryjna do 2000 g.
  14. Waga laboratoryjna do 210g.
  15. pH-metr (zestaw).
  16. Pompa perstaltyczna (10 800 PLN)
  17. Pompa perystaltyczna.
  18. Aparat do pomiaru oddziaływań typu Ligand Tracer (270 000 PLN)
  19. Inkubator z wytrząsaniem do hodowli bakterii (70 000 PLN)
  20. Kolumna chromatograficzna Q 1ML (5 000 PLN)
  21. Mieszadło magnetyczne (3 szt.) (8 118 PLN)

Information in the final report

  • Publication in academic press/journals (24)
  1. A fluorinated indole-based MDM2 antagonist selectively inhibits the growth of p53wt osteosarcoma cells
    Authors:
    Lukasz Skalniak, Aleksandra Twarda-Clapa, Constantinos G. Neochoritis, Ewa Surmiak, Monika Machula, Aneta Wisniewska, Beata Labuzek, Ameena M. Ali, Sylwia Krzanik, Grzegorz Dubin, Matthew Groves, Alexander Dömling, Tad A. Holak
    Academic press:
    The FEBS Journal (rok: 2019, tom: 286, strony: 1360–1374), Wydawca: Wiley
    Status:
    Published
    DOI:
    10.1111/febs.14774 - link to the publication
  2. Optimized Inhibitors of MDM2 via an Attempted Protein-Templated Reductive Amination
    Authors:
    Ramon van der Vlag, M. Yagiz Unver, Tommaso Felicetti, Aleksandra Twarda-Clapa, Fatima Kassim, Cagdas Ermis, Constantinos G. Neochoritis, Bogdan Musielak, Beata Labuzek, Alexander Domling, Tad A. Holak, and Anna K. H. Hirsch
    Academic press:
    ChemMedChem (rok: 2020, tom: 15, strony: 370-375), Wydawca: Wiley
    Status:
    Published
    DOI:
    10.1002/cmdc.201900574 - link to the publication
  3. Small-molecule inhibitors of PD-1/PD-L1 immune checkpoint alleviate the PD-L1-induced exhaustion of T-cells. Oncotarget
    Authors:
    Skalniak, L., Zak, K.M., Guzik, K., Magiera, K., Musielak, B., Pachota, M., Szelazek, B., Kocik, J., Grudnik, P., Tomala, M., Krzanik, S., Pyrc, K., Dömling, A., Dubin, G., Holak, T.A.
    Academic press:
    Oncotarget (rok: 2017, tom: 8, strony: 72167-72181), Wydawca: Impact Journals
    Status:
    Published
    DOI:
    10.18632/oncotarget.20050. - link to the publication
  4. Specific Antibody Fragment Ligand Traps Blocking FGF1 Activity
    Authors:
    Chudzian, Julia; Szlachcic, Anna; Zakrzewska, Malgorzata; et al.
    Academic press:
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (rok: 2018, tom: 19, strony: 2470), Wydawca: MDPI, BASEL, SWITZERLAND
    Status:
    Published
    DOI:
    brak - link to the publication
  5. Systematic 'foldamerization' of peptide inhibiting p53-MDM2/X interactions by the incorporation of trans- or cis-2-aminocyclopentanecarboxylic acid residues
    Authors:
    Paulina Fortuna, Aleksandra Twarda-Cłapa, Łukasz Skalniak, Katarzyna Ożga, Tad A. Holak, Łukasz Berlicki
    Academic press:
    Eur. J. Med. Chem. (rok: 2020, tom: 208, strony: 112814), Wydawca: Elsevier
    Status:
    Published
    DOI:
    10.1016/j.ejmech.2020.112814 - link to the publication
  6. A Unique Mdm2-Binding Mode of the 3‑Pyrrolin-2-one- and 2‑Furanone-Based Antagonists of the p53-Mdm2 Interaction
    Authors:
    Ewa Surmiak, Aleksandra Twarda-Clapa, Krzysztof M. Zak, Bogdan Musielak, Marcin D. Tomala, Katarzyna Kubica, Przemyslaw Grudnik, Mariusz Madej, Mateusz Jablonski, Jan Potempa, Justyna Kalinowska-Tluscik, Alexander Dö mling, Grzegorz Dubin and Tad A. Holak
    Academic press:
    ACS chemical biology (rok: 2016, tom: 11, strony: 3310-3318), Wydawca: American Chemical Society
    Status:
    Published
    DOI:
    10.1021/acschembio.6b00596 - link to the publication
  7. Competition NMR for Detection of Hit/Lead Inhibitors of Protein–Protein Interactions
    Authors:
    Bogdan Musielak, Weronika Janczyk, Ismael Rodriguez, Jacek Plewka, Dominik Sala, Katarzyna Magiera-Mularz, and Tad A. Holak
    Academic press:
    Molecules (rok: 2020, tom: 25, strony: 3017), Wydawca: MDPI
    Status:
    Published
    DOI:
    10.3390/molecules25133017 - link to the publication
  8. Hitting on the move: Targeting intrinsically disordered protein states of the MDM2-p53 interaction
    Authors:
    Constantinos G. Neochoritis, Jack Atmaj, Aleksandra Twarda-Clapa, Ewa Surmiak, Lukasz Skalniak, Lisa-Maria Köhler, Damian Muszak, Katarzyna Kurpiewska, Justyna Kalinowska-Tłuścik, Barbara Beck, Tad A. Holak, Alexander Dömling
    Academic press:
    European Journal of Medicinal Chemistry (rok: 2019, tom: 182, strony: 111588), Wydawca: Elsevier
    Status:
    Published
    DOI:
    10.1016/j.ejmech.2019.111588 - link to the publication
  9. Nanodiamonds as "artificial proteins": Regulation of a cell signalling system using low nanomolar solutions of inorganic nanocrystals
    Authors:
    Balek L, Buchtova M, Kunova Bosakova M, Varecha M, Foldynova-Trantirkova S, Gudernova I, Vesela I, Havlik J, Neburkova J, Turner S, Krzyscik MA, Zakrzewska M, Klimaschewski L, Claus P, Trantirek L, Cigler P, Krejci P.
    Academic press:
    Biomaterials (rok: 2018, tom: 176, strony: 106-121), Wydawca: ELSEVIER
    Status:
    Published
    DOI:
    brak - link to the publication
  10. Rational design and synthesis of 1,5-disubstituted tetrazoles as potent inhibitors of the MDM2-p53 interaction
    Authors:
    Ewa Surmiak , Constantinos G. Neochoritis , Bogdan Musielak , Aleksandra Twarda-Clapa , Katarzyna Kurpiewska, Grzegorz Dubin, Carlos Camacho , Tad A. Holak, Alexander Domling
    Academic press:
    European Journal of Medicinal Chemistry (rok: 2017, tom: 126, strony: 384–407), Wydawca: Elsevier Masson SAS
    Status:
    Published
    DOI:
    brak - link to the publication
  11. Ultrasensitive electrochemical determination of the cancer biomarker protein sPD-L1 based on a BMS-8-modified gold electrode
    Authors:
    Paweł Niedziałkowski, Magdalena Bojko, Jacek Ryl, Anna Wcisło, Marta Spodzieja, Katarzyna Magiera-Mularz, Katarzyna Guzik, Grzegorz Dubin, Tad A. Holak, Tadeusz Ossowski, Sylwia Rodziewicz-Moto
    Academic press:
    Bioelectrochemistry (rok: 2021, tom: 139, strony: 107742), Wydawca: Elsevier
    Status:
    Published
    DOI:
    10.1016/j.bioelechem.2021.107742 - link to the publication
  12. Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists
    Authors:
    Constantinos G. Neochoritis, Maryam Kazemi Miraki, Eman M. M. Abdelraheem, Ewa Surmiak, Tryfon Zarganes-Tzitzikas, Beata Łabuzek, Tad A. Holak, Alexander Dömling
    Academic press:
    Beilstein Journal of Organic Chemistry (rok: 2019, tom: 15, strony: 513–520), Wydawca: Beilstein Institute for the Advancement of Chemical Sciences
    Status:
    Published
    DOI:
    10.3762/bjoc.15.45 - link to the publication
  13. FGF2 Dual Warhead Conjugate with Monomethyl Auristatin E and α-Amanitin Displays a Cytotoxic Effect towards Cancer Cells Overproducing FGF Receptor 1
    Authors:
    Świderska KW, Szlachcic A, Opaliński Ł, Zakrzewska M, Otlewski J.
    Academic press:
    Int J Mol Sci. (rok: 2018, tom: 19 (7), strony: 2098), Wydawca: MDPI, BASEL, SWITZERLAND
    Status:
    Published
    DOI:
    10.3390/ijms19072098 - link to the publication
  14. Helping the Released Guardian: Drug Combinations for Supporting the Anticancer Activity of HDM2 (MDM2) Antagonists
    Authors:
    Justyna Kocik, Monika Machula, Aneta Wisniewska, Ewa Surmiak, Tad A. Holak, Lukasz Skalniak
    Academic press:
    Cancers (rok: 2019, tom: 11, strony: 1014), Wydawca: MDPI
    Status:
    Published
    DOI:
    10.3390/cancers11071014 - link to the publication
  15. Structural Biology of the Immune Checkpoint Receptor PD-1 and Its Ligands PD-L1/PD-L2
    Authors:
    Krzysztof M. Zak Przemyslaw Grudnik Katarzyna Magiera, Alexander Doemling,Grzegorz Dubin and Tad A. Holak
    Academic press:
    Structure (rok: 2017, tom: 25, strony: 1163-1174), Wydawca: Cell Press
    Status:
    Published
    DOI:
    10.1016/j.str.2017.06.011 - link to the publication
  16. Two-Step Synthesis of Complex Artificial Macrocyclic Compounds
    Authors:
    Rudrakshula Madhavachary, Eman M. M. Abdelraheem, Arianna Rossetti, Aleksandra Twarda-Clapa, Bogdan Musielak, Katarzyna Kurpiewska, Justyna Kalinowska- Tłuscik, Tad A. Holak, and Alexander Doemling
    Academic press:
    Angew Chem Int Ed Engl (rok: 2017, tom: 56, strony: 10725 –10729), Wydawca: Wiley-VCH
    Status:
    Published
    DOI:
    10.1002/anie.201704426 - link to the publication
  17. A therapeutic patent overview of MDM2/Xtargeted therapies (2014–2018)
    Authors:
    Lukasz Skalniak, Ewa Surmiak, Tad A. Holak
    Academic press:
    Expert Opinion on Therapeutic Patents (rok: 2019, tom: 29, strony: 151-170), Wydawca: Taylor & Francis
    Status:
    Published
    DOI:
    10.1080/13543776.2019.1582645 - link to the publication
  18. Bioactive Macrocyclic Inhibitors of the PD-1/PD-L1 Immune Checkpoint
    Authors:
    Katarzyna Magiera-Mularz, Lukasz Skalniak, Krzysztof M. Zak, Bogdan Musielak, Ewa Rudzinska-Szostak, Łukasz Berlicki, Justyna Kocik, Przemyslaw Grudnik, Dominik Sala, Tryfon Zarganes-Tzitzikas, Shabnam Shaabani, Alexander Dçmling, Grzegorz Dubin, and Tad A. Holak
    Academic press:
    Angew Chem Int Ed Engl (rok: 2017, tom: 56, strony: 13732 –13735), Wydawca: Wiley-VCH
    Status:
    Published
    DOI:
    10.1002/anie.201707707 - link to the publication
  19. Development and characterization of a new inhibitor of heme oxygenase activity for cancer treatment
    Authors:
    Olga Mucha, Paulina Podkalicka, Maciej Mikulski, Szymon Barwacz, Kalina Andrysiak, Anna Biela, Mateusz Mieczkowski, Neli Kachamakova-Trojanowska, Damian Ryszawy, Arkadiusz Białas, Bożena Szelążek, Przemysław Grudnik, Eliza Majewska, Kinga Michalik, Krzysztof Jakubiec, Marcin Bień, Natalia Witkowska, Karolina Gluza, Dariusz Ekonomiuk, Kamil Sitarz, Michał Gałęzowski, Krzysztof Brzózka, Grzegorz Dubin, Alicja Józkowicz, Józef Dulak, Agnieszka Łoboda
    Academic press:
    Archives of Biochemistry and Biophysics (rok: 2019, tom: 671, strony: 130–142), Wydawca: Elsevier
    Status:
    Published
    DOI:
    10.1016/j.abb.2019.07.002 - link to the publication
  20. Di-Bromo-based small-molecule inhibitors of the PD-1/PD-L1 immune checkpoint
    Authors:
    Konieczny, M., Musielak, B., Kocik, J., Skalniak, L., Sala, D., Czub, M., Magiera-Mularz, K., Rodriguez, I., Holak, T.A., Plewka, J.
    Academic press:
    J. Med. Chem. (rok: 2020, tom: 63,, strony: 11271-11285;), Wydawca: ACS
    Status:
    Published
    DOI:
    10.1021/acs.jmedchem.0c01260. - link to the publication
  21. Immune Checkpoint PD-1/PD-L1: Is There Life Beyond Antibodies?
    Authors:
    Konstantinidou, Markella; Zarganes-Tzitzikas, Tryfon; Magiera-Mularz, Katarzyna et al.
    Academic press:
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (rok: 2018, tom: 57, strony: 4840-4848), Wydawca: Wiley
    Status:
    Published
    DOI:
    10.1002/anie.201710407 - link to the publication
  22. Identification of a peptide antagonist of the FGF1–FGFR1 signaling axis by phage display selection
    Authors:
    Magdalena Lipok, Anna Szlachcic, Kinga Kindela, Aleksandra Czyrek, Jacek Otlewski
    Academic press:
    FEBS Open Bio (rok: 2019, tom: 9, strony: 914–924), Wydawca: FEBS Press
    Status:
    Published
    DOI:
    10.1002/2211-5463.12618 - link to the publication
  23. Small-Molecule Inhibitors of the Programmed Cell Death-1/ Programmed Death-Ligand 1 (PD-1/PD-L1) Interaction via Transiently Induced Protein States and Dimerization of PD-L1
    Authors:
    Katarzyna Guzik, Krzysztof M. Zak,Przemyslaw Grudnik, Katarzyna Magiera, Bogdan Musielak, Ricarda Torner, Lukasz Skalniak, Alexander Doemling, Grzegorz Dubin, and Tad A. Holak
    Academic press:
    J. Med. Chem. (rok: 2017, tom: 60, strony: 5857−5867), Wydawca: American Chemical Society
    Status:
    Published
    DOI:
    10.1021/acs.jmedchem.7b00293 - link to the publication
  24. Structural basis for small molecule targeting of the programmed death ligand 1 (PD-L1)
    Authors:
    Krzysztof M. Zak, Przemyslaw Grudnik, Katarzyna Guzik, Bartosz J. Zieba, Bogdan Musielak, Alexander Dömling, Grzegorz Dubin and Tad A. Holak
    Academic press:
    Oncotarget (rok: 2016, tom: 7 (21), strony: 30323-35), Wydawca: Impact Journals
    Status:
    Published
    DOI:
    10.18632/oncotarget.8730 - link to the publication

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