The interactions of Pu22 G-quadruplex, derived from c-MYC promoter sequence, with antitumor acridine derivatives – an NMR/MD combined study - Publikacja - MOST Wiedzy

Wyszukiwarka

The interactions of Pu22 G-quadruplex, derived from c-MYC promoter sequence, with antitumor acridine derivatives – an NMR/MD combined study

Abstrakt

Unsymmetrical bisacridines (UAs) represent a novel class of anticancer agents that exhibit significant antitumor activity against a wide range of cancer cell lines and solid tumors in vivo. UAs consist of two different acridine-based ring systems, which are connected by an aminoalkyl linker. Recent studies have demonstrated that UAs can suppress the c-MYC protooncogene, which is overexpressed in many tumor types. As a proposed molecular basis for this activity, UAs have been suggested to stabilize the G-quadruplex structure formed within the promoter region of c-MYC. In this study, we performed spectroscopic and computational analyses to investigate the stereochemistry of the c-MYC NHE III1 representative G-quadruplex, codenamed Pu22, in complex with two promising bisacridines, C-2045 and C-2053, as well as their monomeric counterparts, C-1311 and C-1748. C-1311 formed a well-defined 1:2 mol/mol DNA:ligand non-covalent adduct, whose solution structure was determined via 2D NMR. In contrast, C-1748 displayed weak and nonspecific interactions with the Pu22 G-quadruplex. Finally, the Pu22:UAs complexes were examined using a combination of NMR and molecular modeling approaches, including umbrella sampling simulations. These results provide insights into the interaction mechanisms of UAs with G-quadruplex structures and highlight their potential as therapeutic agents targeting c-MYC.

Cytowania

  • 0

    CrossRef

  • 0

    Web of Science

  • 0

    Scopus

Cytuj jako

Pełna treść

pełna treść publikacji nie jest dostępna w portalu

Słowa kluczowe

Informacje szczegółowe

Kategoria:
Publikacja w czasopiśmie
Typ:
artykuły w czasopismach
Opublikowano w:
Molecular Therapy-Nucleic Acids nr 36,
ISSN: 2162-2531
Język:
angielski
Rok wydania:
2025
Opis bibliograficzny:
Laskowski T., Kosno M., Andrałojć W., Pakuła J., Stojałowski R., Borzyszkowska-Bukowska J., Paluszkiewicz E., Mazerska Z.: The interactions of Pu22 G-quadruplex, derived from c-MYC promoter sequence, with antitumor acridine derivatives – an NMR/MD combined study// Molecular Therapy-Nucleic Acids -,iss. 2 (2025), s.102513-
DOI:
Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1016/j.omtn.2025.102513
Źródła finansowania:
  • IDUB
Weryfikacja:
Politechnika Gdańska

wyświetlono 0 razy

Publikacje, które mogą cię zainteresować

Meta Tagi