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Abstract
In this work, we present studies on relatively new and still not well-explored potential anticancer targets which are shelterin proteins, in particular the TRF1 protein can be blocked by in silico designed "peptidomimetic" molecules. TRF1 interacts directly with the TIN2 protein, and this protein-protein interaction is crucial for the proper functioning of telomere, which could be blocked by our novel modified peptide molecules. Our chemotherapeutic approach is based on assumption that modulation of TRF1-TIN2 interaction may be more harmful for cancer cells as cancer telomeres are more fragile than in normal cells. We have shown in vitro within SPR experiments that our modified peptide PEP1 molecule interacts with TRF1, presumably at the site originally occupied by the TIN2 protein. Disturbance of the shelterin complex by studied molecule may not in short term lead to cytotoxic effects, however blocking TRF1-TIN2 resulted in cellular senescence in cellular breast cancer lines used as a cancer model. Thus, our compounds appeared useful as starting model compounds for precise blockage of TRF proteins.
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Authors (15)
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Umesh Kalathiya
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Monikaben Padariya
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Katarzyna Wegrzyn
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Maciej Prusinowski
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Joanna Żebrowska
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Agnieszka Zylicz-Stachula
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Piotr Skowron prof. dr hab.
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Marek Drab
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Mariusz Szajewski
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Maciej Ciesielski
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Małgorzata Gawrońska
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Mariusz Makowski dr
Cite as
Full text
- Publication version
- Accepted or Published Version
- DOI:
- Digital Object Identifier (open in new tab) 10.1002/chem.202300970
- License
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Details
- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
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CHEMISTRY-A EUROPEAN JOURNAL
no. 29,
pages 1 - 21,
ISSN: 0947-6539 - Language:
- English
- Publication year:
- 2023
- Bibliographic description:
- Brankiewicz W., Kalathiya U., Padariya M., Wegrzyn K., Prusinowski M., Żebrowska J., Zylicz-Stachula A., Skowron P., Drab M., Szajewski M., Ciesielski M., Gawrońska M., Kallingal A., Makowski M., Bagiński M.: Modified Peptide Molecules As Potential Modulators of Shelterin Protein Functions; TRF1// CHEMISTRY-A EUROPEAN JOURNAL -Vol. 29,iss. 55 (2023), s.1-21
- DOI:
- Digital Object Identifier (open in new tab) 10.1002/chem.202300970
- Sources of funding:
-
- COST_FREE
- Verified by:
- Gdańsk University of Technology
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