Structural basis of bis-quinolinium ligands binding to quadruplex–duplex hybrids from PIM1 oncogene

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F25%3A73635236" target="_blank" >RIV/61989592:15310/25:73635236 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15640/25:73635236

Result on the web

<a href="https://academic.oup.com/nar/article/53/17/gkaf894/8251892" target="_blank" >https://academic.oup.com/nar/article/53/17/gkaf894/8251892</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/nar/gkaf894" target="_blank" >10.1093/nar/gkaf894</a>

Result language

angličtina

Original language name

Structural basis of bis-quinolinium ligands binding to quadruplex–duplex hybrids from PIM1 oncogene

Original language description

Our study investigates the interaction of two bis-quinolinium ligands, Phen-DC3 and 360A, with the quadruplex–duplex hybrid (QDH) derived from the promoter region of the PIM1 oncogene. While the QDH is polymorphic in vitro, with a hybrid and antiparallel conformation, we demonstrate that it predominantly adopts the antiparallel conformation within the intracellular environment of Xenopus laevis oocytes (eukaryotic model system). Notably, both ligands selectively bind to the hybrid QDH conformation in vitro and in a cellular context. High-resolution nuclear magnetic resonance (NMR) structures of the complexes between the hybrid QDH and the ligands reveal distinct binding modes at the quadruplex–duplex (Q-D) junction. Specifically, Phen-DC3 binds rigidly, while 360A dynamically reorients between two positions. Our findings provide a crucial paradigm highlighting the differences in structural equilibria involving QDH in vitro compared to its behavior in the intracellular space. They also underscore the potential to modulate these equilibria under native-like conditions through ligand interactions. The observed differences in the binding of Phen-DC3 and 360A lay the groundwork for designing next-generation bis-quinolinium compounds with enhanced selectivity for the Q-D junction. Methodologically, our study illustrates the potential of &lt;sup&gt;19&lt;/sup&gt;F-detected in-cell NMR methodology for screening interactions between DNA targets and drug-like molecules under physiological conditions.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10403 - Physical chemistry

Project

—

Continuities

R - Projekt Ramcoveho programu EK

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

NUCLEIC ACIDS RESEARCH

ISSN

—

e-ISSN

1362-4962

Volume of the periodical

53

Issue of the periodical within the volume

17

Country of publishing house

GB - UNITED KINGDOM

Number of pages

17

Pages from-to

"gkaf894-1"-"gkaf894-17"

UT code for WoS article

001573711300001

EID of the result in the Scopus database

2-s2.0-105016474974