Influence of ions, pH and crowding agents on structure and stability of PIM1 secondary structures

Date

2026-08-01

Author

Göller, İrem
Orouji, Saba
Persil Çetinkol, Özgül

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Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer defined by the absence of ER, PR and HER-2 receptors. The lacking of these receptors limits the availability of the targeted therapy options. The recent identification of G-quadruplex-duplex hybrid (QDH) structures within PIM1 oncogenes, which are overexpressed in TNBC tumors, has highlighted their plausible potential as novel therapeutic targets for the treatment of TNBC. Herein, the effect of pH, ions and the molecular crowding on the selected PIM1 secondary structures was investigated in vitro using PAGE, UV-Vis and CD spectroscopy. The G-quadruplex (G4), i-motif (iM) and double helical DNA (dsDNA) structures formed by the selected PIM1 sequences were found to be stable under the investigated conditions and are likely to coexist specially under the acidic conditions. The lower pH was found to be stabilizing the iM structure. K+ ions exhibited a stronger stabilizing effect on G4 structures than Na+ ions. CD results suggested that molecular crowding alters the G4 structure in a cation-dependent manner, whereas the iM remained largely unaffected. Furthermore, the results demonstrated that molecular crowding stabilizes G-quadruplexes, but has a variable effect on i-motif and dsDNA stability based on their molecular weight. These findings may aid in modulating G4, iM, dsDNA, and QDH structures and the development of small molecules designed to target these structures, thereby contributing to future anticancer therapeutic strategies.

Subject Keywords

Breast cancer, G-quadruplex, I-motif, PIM1

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https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=105040130158&origin=inward
https://hdl.handle.net/11511/119542

Collections

Department of Chemistry, Article