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Modified Peptide Molecules As Potential Modulators of Shelterin Protein Functions; TRF1

Abstrakt

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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Wersja publikacji
Accepted albo Published Version
DOI:
Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1002/chem.202300970
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Creative Commons: CC-BY otwiera się w nowej karcie

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Kategoria:
Publikacja w czasopiśmie
Typ:
artykuły w czasopismach
Opublikowano w:
CHEMISTRY-A EUROPEAN JOURNAL nr 29, strony 1 - 21,
ISSN: 0947-6539
Język:
angielski
Rok wydania:
2023
Opis bibliograficzny:
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:
Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1002/chem.202300970
Źródła finansowania:
  • COST_FREE
Weryfikacja:
Politechnika Gdańska

wyświetlono 44 razy

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